铅、镉、铬、汞对大鼠听力的损伤及铜、锰、锌、硒的保护作用研究
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摘要
目的评价重金属铅、汞、铬和镉对听力的影响及铜锰锌硒对铅汞铬镉毒性的拮抗作用。铅、汞、铬和镉是常见的环境污染物,它们进入机体后可引起各种毒性作用,均可能对听力造成损害。铜锰锌硒是生物的必须微量元素,铅、汞、铬和镉的过量摄入可影响人体铜锰锌硒水平;反之,铜锰锌硒又能促进铅、汞、铬和镉的排泄,减轻它们的毒性。本实验旨在研究铅、汞、铬和镉中毒对大鼠听觉系统的影响以及铜锰锌硒对铅、汞、铬和镉毒性的拮抗作用;探讨了铅、汞、铬和镉毒性和铜锰锌硒拮抗作用可能的机理,提示铜锰锌硒可能在一定程度上减轻铅、汞、铬和镉导致的听力损伤。
方法
1.动物模型的建立
健康Wistar大鼠170只,雌雄各85只,140-270g,随机分为34组,
1.1正常对照组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组,正常饲料和生理盐水喂养;
1.2铅染毒组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以醋酸铅(4mg/kg,以铅计,下同)灌胃30天,正常饲料和去离子水喂养。
1.3铜(染铅)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以醋酸铅(4mg/kg)和硫酸铜(2mg/kg,以铜计,下同)灌胃30天,正常饲料和去离子水喂养。
1.4锰(染铅)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以醋酸铅(4mg/kg)和硫酸锰(2mg/kg,以锰计,下同)灌胃30天,正常饲料和去离子水喂养。
1.5染镉组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化镉(4mg/kg,以镉计,下同)灌胃30天,正常饲料和去离子水喂养。
1.6铜(染镉)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化镉(4mg/kg)和硫酸铜(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.7锰(染镉)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化镉(4mg/kg)和硫酸锰(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.8染铬组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg,以铬计,下同)灌胃30天,正常饲料和去离子水喂养。
1.9锌(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg)和硫酸锌(4mg/kg,以锌计,下同)灌胃30天,正常饲料和去离子水喂养。
1.10硒(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg)和亚硒酸钠(2mg/kg,以硒计,下同)灌胃30天,正常饲料和去离子水喂养。
1.11铜(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg)和硫酸铜(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.12锰(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。:以重铬酸钾(4mg/kg)和硫酸锰(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.13染汞组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化汞(4mg/kg,以汞计,下同)灌胃30天,正常饲料和去离子水喂养。
1.14锌(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。:以氯化汞(4mg/kg)和硫酸锌(4mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.15硒(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化汞(4mg/kg)和亚硒酸钠(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.16铜(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化汞(4mg/kg)和硫酸铜(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.17锰(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。:以氯化汞(4mg/kg)和硫酸锰(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
2.听觉脑干诱发电位(auditory brainstem response,ABR)测定
测定各组大鼠听觉脑干诱发电位,观察Ⅰ波的潜伏期。将各组大鼠用水合氯醛腹腔注射麻醉,于测听室将接地电极插至乳突,记录电极插至头顶,参考电极插至耳内,给予不同声强的刺激,记录90dB和60dB刺激下听觉脑干电诱发电位图(ABR)及其Ⅰ波潜伏期数值。
结果
1.对照组大鼠听觉脑干电诱发电位图(ABR)非常清晰,各个波形较为明显,Ⅰ波潜伏期较短,听力正常。
2.染铅组听觉脑干电诱发电位图(ABR)较为紊乱,听觉脑干电诱发电位图只能勉强辨认出波形,但Ⅰ波的潜伏期远远比对照组长,说明染铅组大鼠听力已经受到严重损伤。
3.铜(染铅)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明铜对铅中毒引起的听力损伤有明显的保护作用。
4.锰(染铅)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明锰对铅中毒引起的听力损伤也有明显的保护作用。
5.染镉组听觉脑干电诱发电位图(ABR)只能勉强辨认出波形,Ⅰ波的潜伏期已经远比对照组长,说明染镉组大鼠听力已经受到严重损伤。
6.铜(染镉)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,说明铜对镉中毒引起的听力损伤有明显的保护作用。
7.锰(染镉)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期接近正常,说明锰对镉中毒引起的听力损伤也有明显的保护作用。
8.染铬组听觉脑干电诱发电位图(ABR)较为紊乱,听觉脑干电诱发电位图只能勉强辨认出波形,但Ⅰ波的潜伏期远远比对照组长,说明染铬组大鼠听力已经受到严重损伤。
9.锌(染铬)保护组听觉脑干电诱发电位图(ABR)波形较为紊乱,Ⅰ波只能勉强辨认,听力恢复不理想,说明锌对铬中毒引起的听力损伤的保护作用不明显。
10.硒(染铬)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明硒对铬中毒引起的听力损伤也有明显的保护作用。
11.铜(染铬)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明铜对铬中毒引起的听力损伤有明显的保护作用。
12.锰(染铬)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明锰对铬中毒引起的听力损伤也有明显的保护作用。
13.染汞组听觉脑干电诱发电位图(ABR)较为紊乱,听觉脑干电诱发电位图只能勉强辨认出波形,但Ⅰ波的潜伏期远远比对照组长,说明染汞组大鼠听力已经受到严重损伤。
14.铜(染汞)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明铜对汞中毒引起的听力损伤有明显的保护作用。
15.锰(染汞)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明锰对汞中毒引起的听力损伤也有明显的保护作用。
16.锌(染汞)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明锌对汞中毒引起的听力损伤有明显的保护作用。
17.硒(染汞)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明硒对汞中毒引起的听力损伤也有明显的保护作用。
结论
铅、镉、铬、汞均能对大鼠听力造成一定伤害,而铜、锰、锌、硒对此种伤害表现出一定的保护作用,提示在一定程度上铜、锰、锌、硒能拮抗铅镉铅、镉、铬、汞的毒性作用,减轻铅、镉、铬、汞对听力的损害。
Objective
To evaluate effects on auditory changes caused by heavy metal lead,cadmium, chromium or mercury and the contradict effects of zinc,selenium,copper and manganese.Lead,cadmium,chromium and mercury are common pollutants in nature and they could cause variety toxicities and damage hearing functions after entering organism.Zinc,selenium,copper and manganese are essential microelements,excess intake of lead,cadmium,chromium or mercury ions would influence the level of zinc, selenium,copper or manganese ions in organism;otherwise the appropriate amount of zinc,selenium,copper or manganese could enhance the excretions of lead,cadmium, chromium or mercury to relieve toxicities of them.The aim of this study is to study the effects of lead,cadmium,chromium or mercury on rats hearing system and the contradict effects of zinc,selenium,copper or manganese on them;at the same time, we also approached the probable mechanisms of toxicities of lead,cadmium, chromium or mercury and contradict effects of zinc,selenium,copper or manganese. Results show that zinc,selenium,copper or manganese could relieve hearing injuries caused by lead,cadmium,chromium or mercury.
Methods
1.ANIMAL TREATMENT
170 Wistar rats weighing 140-270g,85 female and male separately,were divided randomly into 34 groups and were administered different drugs through intragastric administration according to different groups and dosages,and the changes of rats in physical sign,behavior and weight were observed.
1.1 Control groups:5 male and 5 female rats in these groups were feed with common feedstuff and saline water.
1.2 Lead-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg lead acetate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.3 Copper protective groups(lead-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg lead acetate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.4 Manganese protective groups(lead-exposed):5 male and 5 female rats in these groups were subjected to 4mg/kg lead acetate and 2mg/kg manganese sulfate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.5 Cadmium-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg cadmium chloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.6 Copper protective groups(cadmium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg cadmium chloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.7 Manganese protective groups(cadmium-exposed):5 male and 5 female rats in these groups Were subjected to 2mg/kg manganese sulfate and 4mg/kg cadmium chloride for 30 days,and feed with common feedstuff and deionized water.
1.8 Chromium-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg potassium dichromate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.9 Copper protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg potassium dichromate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.10 Manganese protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg manganese sulfate and 4mg/kg potassium dichromate for 30 days,and feed with common feedstuff and deionized water.
1.11 Zinc protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg zinc sulfate and 4mg/kg potassium dichromate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.12 Selenium protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg sodium selenite and 4mg/kg potassium dichromate for 30 days,and feed with common feedstuff and deionized water.
1.13 Mercury-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg mercury bichloride through intragastric administration for 30 days, and feed with common feedstuff and deionized water.
1.14 Copper protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg mercury bichloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.15 Manganese protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg manganese sulfate and 4mg/kg mercury bichloride for 30 days,and feed with common feedstuff and deionized water.
1.16 Zinc protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg zinc sulfate and 4mg/kg mercury bichloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.17 Selenium protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg sodium selenite and 4mg/kg mercury bichloride for 30 days,and feed with common feedstuff and deionized water.
2.Measurement of auditory brainstem response(ABR)
ABR and the latency of waveⅠwere measured.Each group of rats was anesthetized by pentobarbital sodium,ABR and the latency of waveⅠof 90db and 60db stimuli were recorded by inserting ground electrode into temporal apophysis, recording electrode into cupular part of head and reference electrode into the ear.
Results
1.ABR figures and waveforms of control groups were normal and clear,the latencies of waveⅠwere short,showing that the hearing functions is normal in rats.
2.ABR figures and waveforms of lead-exposed groups were hard to identify, further more,the latencies of waveⅠwere prolonged than that of control groups, showing that lead exposing caused serious hearing loses in rats.
3.ABR figures and waveforms of copper protective(lead-exposed)groups were relatively clear,the latencies of waveⅠwere approximately the same to that of normal latency,showing that the hearing functions were partly recovered in rats of copper protective groups to that of lead-exposed groups.
4.ABR figures and waveforms of manganese protective(lead-exposed)groups were relatively clear,the latencies of waveⅠwere approximately the same to that of normal latency,showing that the hearing functions were partly recovered in rats of manganese protective groups to that of lead-exposed groups.
5.ABR figures and waveforms of cadmium-exposed groups were merely identified,and the latencies of waveⅠwere prolonged than that of control groups. Results show that hearing functions in this group were seriously damaged by cadmium.
6.ABR figures and waveforms of copper protective(cadmium-exposed)groups were relatively clear,the latencies of waveⅠwere approximately the same to that of normal latency which show that copper has protective effects on damages of hearing functions caused by cadmium.
7.ABR figures and waveforms were also relatively normal in manganese protective groups(cadmium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that manganese has protective effects on damages of hearing functions caused by cadmium.
8.ABR figures and waveforms were merely identified in chromium-exposed groups,and the latencies of waveⅠwas prolonged than that of control groups. Results show that hearing functions in this group were seriously damaged by chromium.
9.ABR figures and waveforms were relatively normal in copper protective groups (chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that copper has protective effects on damages of hearing functions caused by chromium.
10.ABR figures and waveforms were also relatively normal in manganese protective groups(chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that manganese has protective effects on damages of hearing functions caused by chromium.
11.ABR figures and waveforms were relatively normal in zinc protective groups (chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that zinc has protective effects on damages of hearing functions caused by chromium.
12.ABR figures and waveforms were also relatively normal in selenium protective groups(chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that selenium has protective effects on damages of hearing functions caused by chromium.
13.ABR figures and waveforms were merely identified in mercury-exposed groups, and the latencies of waveⅠwere prolonged than that of control groups.Results show that hearing functions in this group were seriously damaged by mercury.
14.ABR figures and waveforms were relatively normal in copper protective groups (mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that copper has protective effects on damages of hearing functions caused by mercury.
15.ABR figures and waveforms were also relatively normal in manganese protective groups(mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that manganese has protective effects on damages of hearing functions caused by mercury.
16.ABR figures and waveforms were relatively normal in zinc protective groups (mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that zinc has protective effects on damages of hearing functions caused by mercury.
17.ABR figures and waveforms were also relatively normal in selenium protective groups(mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that selenium has protective effects on damages of hearing functions caused by mercury.
Conclusions
Hearing functions of rats could be partly damaged by been exposed to lead, cadmium,chromium and mercury,and zinc,selenium,copper and manganese showed some protective effects on the damages caused by them,hint that zinc, selenium,copper or manganese has some contradict effects to the toxicities of lead, cadmium,chromium or mercury to the hearing losses in rats,and partly relieve the impairment to hearing functions caused by them.
方法
1.动物模型的建立
健康Wistar大鼠170只,雌雄各85只,140-270g,随机分为34组,
1.1正常对照组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组,正常饲料和生理盐水喂养;
1.2铅染毒组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以醋酸铅(4mg/kg,以铅计,下同)灌胃30天,正常饲料和去离子水喂养。
1.3铜(染铅)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以醋酸铅(4mg/kg)和硫酸铜(2mg/kg,以铜计,下同)灌胃30天,正常饲料和去离子水喂养。
1.4锰(染铅)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以醋酸铅(4mg/kg)和硫酸锰(2mg/kg,以锰计,下同)灌胃30天,正常饲料和去离子水喂养。
1.5染镉组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化镉(4mg/kg,以镉计,下同)灌胃30天,正常饲料和去离子水喂养。
1.6铜(染镉)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化镉(4mg/kg)和硫酸铜(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.7锰(染镉)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化镉(4mg/kg)和硫酸锰(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.8染铬组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg,以铬计,下同)灌胃30天,正常饲料和去离子水喂养。
1.9锌(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg)和硫酸锌(4mg/kg,以锌计,下同)灌胃30天,正常饲料和去离子水喂养。
1.10硒(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg)和亚硒酸钠(2mg/kg,以硒计,下同)灌胃30天,正常饲料和去离子水喂养。
1.11铜(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以重铬酸钾(4mg/kg)和硫酸铜(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.12锰(染铬)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。:以重铬酸钾(4mg/kg)和硫酸锰(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.13染汞组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化汞(4mg/kg,以汞计,下同)灌胃30天,正常饲料和去离子水喂养。
1.14锌(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。:以氯化汞(4mg/kg)和硫酸锌(4mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.15硒(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化汞(4mg/kg)和亚硒酸钠(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.16铜(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。以氯化汞(4mg/kg)和硫酸铜(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
1.17锰(染汞)保护组雌Wistar大鼠5只为一组,雄Wistar大鼠5只为一组。:以氯化汞(4mg/kg)和硫酸锰(2mg/kg)灌胃30天,正常饲料和去离子水喂养。
2.听觉脑干诱发电位(auditory brainstem response,ABR)测定
测定各组大鼠听觉脑干诱发电位,观察Ⅰ波的潜伏期。将各组大鼠用水合氯醛腹腔注射麻醉,于测听室将接地电极插至乳突,记录电极插至头顶,参考电极插至耳内,给予不同声强的刺激,记录90dB和60dB刺激下听觉脑干电诱发电位图(ABR)及其Ⅰ波潜伏期数值。
结果
1.对照组大鼠听觉脑干电诱发电位图(ABR)非常清晰,各个波形较为明显,Ⅰ波潜伏期较短,听力正常。
2.染铅组听觉脑干电诱发电位图(ABR)较为紊乱,听觉脑干电诱发电位图只能勉强辨认出波形,但Ⅰ波的潜伏期远远比对照组长,说明染铅组大鼠听力已经受到严重损伤。
3.铜(染铅)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明铜对铅中毒引起的听力损伤有明显的保护作用。
4.锰(染铅)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明锰对铅中毒引起的听力损伤也有明显的保护作用。
5.染镉组听觉脑干电诱发电位图(ABR)只能勉强辨认出波形,Ⅰ波的潜伏期已经远比对照组长,说明染镉组大鼠听力已经受到严重损伤。
6.铜(染镉)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,说明铜对镉中毒引起的听力损伤有明显的保护作用。
7.锰(染镉)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期接近正常,说明锰对镉中毒引起的听力损伤也有明显的保护作用。
8.染铬组听觉脑干电诱发电位图(ABR)较为紊乱,听觉脑干电诱发电位图只能勉强辨认出波形,但Ⅰ波的潜伏期远远比对照组长,说明染铬组大鼠听力已经受到严重损伤。
9.锌(染铬)保护组听觉脑干电诱发电位图(ABR)波形较为紊乱,Ⅰ波只能勉强辨认,听力恢复不理想,说明锌对铬中毒引起的听力损伤的保护作用不明显。
10.硒(染铬)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明硒对铬中毒引起的听力损伤也有明显的保护作用。
11.铜(染铬)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明铜对铬中毒引起的听力损伤有明显的保护作用。
12.锰(染铬)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明锰对铬中毒引起的听力损伤也有明显的保护作用。
13.染汞组听觉脑干电诱发电位图(ABR)较为紊乱,听觉脑干电诱发电位图只能勉强辨认出波形,但Ⅰ波的潜伏期远远比对照组长,说明染汞组大鼠听力已经受到严重损伤。
14.铜(染汞)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明铜对汞中毒引起的听力损伤有明显的保护作用。
15.锰(染汞)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明锰对汞中毒引起的听力损伤也有明显的保护作用。
16.锌(染汞)保护组听觉脑干电诱发电位图(ABR)波形较为明显,Ⅰ波潜伏期接近正常,听力得到一定的恢复,说明锌对汞中毒引起的听力损伤有明显的保护作用。
17.硒(染汞)保护组听觉脑干电诱发电位图(ABR)波形也较为清晰,Ⅰ波潜伏期也接近正常,听力也有一定的恢复,说明硒对汞中毒引起的听力损伤也有明显的保护作用。
结论
铅、镉、铬、汞均能对大鼠听力造成一定伤害,而铜、锰、锌、硒对此种伤害表现出一定的保护作用,提示在一定程度上铜、锰、锌、硒能拮抗铅镉铅、镉、铬、汞的毒性作用,减轻铅、镉、铬、汞对听力的损害。
Objective
To evaluate effects on auditory changes caused by heavy metal lead,cadmium, chromium or mercury and the contradict effects of zinc,selenium,copper and manganese.Lead,cadmium,chromium and mercury are common pollutants in nature and they could cause variety toxicities and damage hearing functions after entering organism.Zinc,selenium,copper and manganese are essential microelements,excess intake of lead,cadmium,chromium or mercury ions would influence the level of zinc, selenium,copper or manganese ions in organism;otherwise the appropriate amount of zinc,selenium,copper or manganese could enhance the excretions of lead,cadmium, chromium or mercury to relieve toxicities of them.The aim of this study is to study the effects of lead,cadmium,chromium or mercury on rats hearing system and the contradict effects of zinc,selenium,copper or manganese on them;at the same time, we also approached the probable mechanisms of toxicities of lead,cadmium, chromium or mercury and contradict effects of zinc,selenium,copper or manganese. Results show that zinc,selenium,copper or manganese could relieve hearing injuries caused by lead,cadmium,chromium or mercury.
Methods
1.ANIMAL TREATMENT
170 Wistar rats weighing 140-270g,85 female and male separately,were divided randomly into 34 groups and were administered different drugs through intragastric administration according to different groups and dosages,and the changes of rats in physical sign,behavior and weight were observed.
1.1 Control groups:5 male and 5 female rats in these groups were feed with common feedstuff and saline water.
1.2 Lead-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg lead acetate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.3 Copper protective groups(lead-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg lead acetate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.4 Manganese protective groups(lead-exposed):5 male and 5 female rats in these groups were subjected to 4mg/kg lead acetate and 2mg/kg manganese sulfate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.5 Cadmium-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg cadmium chloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.6 Copper protective groups(cadmium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg cadmium chloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.7 Manganese protective groups(cadmium-exposed):5 male and 5 female rats in these groups Were subjected to 2mg/kg manganese sulfate and 4mg/kg cadmium chloride for 30 days,and feed with common feedstuff and deionized water.
1.8 Chromium-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg potassium dichromate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.9 Copper protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg potassium dichromate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.10 Manganese protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg manganese sulfate and 4mg/kg potassium dichromate for 30 days,and feed with common feedstuff and deionized water.
1.11 Zinc protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg zinc sulfate and 4mg/kg potassium dichromate through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.12 Selenium protective groups(chromium-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg sodium selenite and 4mg/kg potassium dichromate for 30 days,and feed with common feedstuff and deionized water.
1.13 Mercury-exposed groups:5 male and 5 female rats in these groups were subjected to 4mg/kg mercury bichloride through intragastric administration for 30 days, and feed with common feedstuff and deionized water.
1.14 Copper protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg copper sulfate and 4mg/kg mercury bichloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.15 Manganese protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg manganese sulfate and 4mg/kg mercury bichloride for 30 days,and feed with common feedstuff and deionized water.
1.16 Zinc protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg zinc sulfate and 4mg/kg mercury bichloride through intragastric administration for 30 days,and feed with common feedstuff and deionized water.
1.17 Selenium protective groups(mercury-exposed):5 male and 5 female rats in these groups were subjected to 2mg/kg sodium selenite and 4mg/kg mercury bichloride for 30 days,and feed with common feedstuff and deionized water.
2.Measurement of auditory brainstem response(ABR)
ABR and the latency of waveⅠwere measured.Each group of rats was anesthetized by pentobarbital sodium,ABR and the latency of waveⅠof 90db and 60db stimuli were recorded by inserting ground electrode into temporal apophysis, recording electrode into cupular part of head and reference electrode into the ear.
Results
1.ABR figures and waveforms of control groups were normal and clear,the latencies of waveⅠwere short,showing that the hearing functions is normal in rats.
2.ABR figures and waveforms of lead-exposed groups were hard to identify, further more,the latencies of waveⅠwere prolonged than that of control groups, showing that lead exposing caused serious hearing loses in rats.
3.ABR figures and waveforms of copper protective(lead-exposed)groups were relatively clear,the latencies of waveⅠwere approximately the same to that of normal latency,showing that the hearing functions were partly recovered in rats of copper protective groups to that of lead-exposed groups.
4.ABR figures and waveforms of manganese protective(lead-exposed)groups were relatively clear,the latencies of waveⅠwere approximately the same to that of normal latency,showing that the hearing functions were partly recovered in rats of manganese protective groups to that of lead-exposed groups.
5.ABR figures and waveforms of cadmium-exposed groups were merely identified,and the latencies of waveⅠwere prolonged than that of control groups. Results show that hearing functions in this group were seriously damaged by cadmium.
6.ABR figures and waveforms of copper protective(cadmium-exposed)groups were relatively clear,the latencies of waveⅠwere approximately the same to that of normal latency which show that copper has protective effects on damages of hearing functions caused by cadmium.
7.ABR figures and waveforms were also relatively normal in manganese protective groups(cadmium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that manganese has protective effects on damages of hearing functions caused by cadmium.
8.ABR figures and waveforms were merely identified in chromium-exposed groups,and the latencies of waveⅠwas prolonged than that of control groups. Results show that hearing functions in this group were seriously damaged by chromium.
9.ABR figures and waveforms were relatively normal in copper protective groups (chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that copper has protective effects on damages of hearing functions caused by chromium.
10.ABR figures and waveforms were also relatively normal in manganese protective groups(chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that manganese has protective effects on damages of hearing functions caused by chromium.
11.ABR figures and waveforms were relatively normal in zinc protective groups (chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that zinc has protective effects on damages of hearing functions caused by chromium.
12.ABR figures and waveforms were also relatively normal in selenium protective groups(chromium-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that selenium has protective effects on damages of hearing functions caused by chromium.
13.ABR figures and waveforms were merely identified in mercury-exposed groups, and the latencies of waveⅠwere prolonged than that of control groups.Results show that hearing functions in this group were seriously damaged by mercury.
14.ABR figures and waveforms were relatively normal in copper protective groups (mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that copper has protective effects on damages of hearing functions caused by mercury.
15.ABR figures and waveforms were also relatively normal in manganese protective groups(mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that manganese has protective effects on damages of hearing functions caused by mercury.
16.ABR figures and waveforms were relatively normal in zinc protective groups (mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency which show that zinc has protective effects on damages of hearing functions caused by mercury.
17.ABR figures and waveforms were also relatively normal in selenium protective groups(mercury-exposed)and the latencies of waveⅠwere approximately the same to that of normal latency.Results show that selenium has protective effects on damages of hearing functions caused by mercury.
Conclusions
Hearing functions of rats could be partly damaged by been exposed to lead, cadmium,chromium and mercury,and zinc,selenium,copper and manganese showed some protective effects on the damages caused by them,hint that zinc, selenium,copper or manganese has some contradict effects to the toxicities of lead, cadmium,chromium or mercury to the hearing losses in rats,and partly relieve the impairment to hearing functions caused by them.
引文
[1]陈建青,锌对镉毒性的拮抗作用.国外医学卫生学分册 1990.17(5).279-282
[2]李红军,白忠贞,王桂敏,童振,李茂进.锌、硒单独与联合作用对镉毒性拮抗作用的研究。职业医学 1997,24(3),9-11
[3]王世俊.金属中毒.第二版,北京:人民卫生出版社,1988,215.
[4]刘爱萍,赵金垣,刘亚宁,赵新华,龙曼海.锌对急性镉中毒性肾损伤保护作用的研究.中国工业医学杂志 1999,12(3),132-135.
[5]刘爱萍,赵金垣,刘亚宁,赵新华,邵涵如,龙曼海.硒对急性镉中毒性肾损伤保护作用的研究.中国工业医学杂志 1997,10(4)193-197.
[6]Volkmar,Cook EH,Pomeroy J et al.Practice parameters for the assessment and treatment of children,adolescents,and adults with autism and other pervasive developmental disorders.J Am Acad Child Adolesc Psychiatry.1999,38:12.
[7]Gillberg C,Wing L.Autism not an extremely rare disorder(Re2 view article).Acta Psychiatry Scand,1999,99:399-400.
[8]Donaldson W.E.and Leemina T.K.Toxlcal Appl.pharmical,1984,73:119.
[9]Stacey N H,Cantilena L R,Klaassen C D,et al.Cadmium toxicity and lipid peroxidation in iso lated rat hepatocytes.Toxicol Appl Pharmacol,1980,53:470.
[10]张献清.金属中毒与脂质过氧化.工业卫生与职业病,1992,18(4):246.
[11]陈建青.锌对镉毒性的拮抗作用.国外医学卫生学分册,1990,5:279.
[12]杨成峰.硒镉相互作用的研究进展.国外医学卫生学分册,1992,2:76.
[13]Gozdzik-Zolnierkiewiez,Moszynski B.Nerve in experimental lead poisoning [J].Acta Otolaryngologoca,1969,68:85-89.
[14]Schwartz J,Otto D.Blood lead hearing thresholds and neuro behavioral development in children and youths.
[15]Schwart J,Otto D.Lead and minor hearing impairment[J].Arch Environ Health,1991,46(5):300-305.
[16]Dietrich KN,Succop PA,Berger OG,et al.Lead exposure and the central auditory processing abilities and cognitive development of urban children:the Cincinnati lead study cohortatage 5 years[J].Neuro toxicol Teratol,1992,14:51-56.
[17]Forst LS,Freels S,Persky V.Occupational lead exposure and hearing loss[J].J OEM,1997,39:658-660.
[18]Meijerman I,Blom WM,deBont HJ,et al.Analysis of differential effects of Pb~(2+)on protein kinase C isozymes[J].Toxicol Appl Pharmacol,1999,156:40-45.
[19]Cremin JD Jr,Smith DR.In vitro vs in vivo Pb effects on brain protein kinase C activity[J].Environ Res,2002,90:191-199.
[20]颜崇淮,沈晓明,吴圣楣.铅对未成熟脑神经毒性机制的研究进展[J].国外医学儿科学分册,1997,24:129-132.
[21]Bouton CM,Frelin LP,Forde CE,et al.Synaptotagmin Ⅰ is a molecular target for lead[J].J Neurochem,2001,76:1724-1735.
[22]付大干,李华强.铅对未成熟脑发育的影响及其作用机制的研究进展[J].中华劳动卫生职业病杂志,2001,19:149-151.
[23]Nihei MK,Desmond NL,McGlothan JL,et al.N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficitsof long-term potentiation and spatial learning[J].Neuroscience,2000,99:233-242.
[24]Guilarte TR,McGlothan JL,Nihei MK.Hippocampal expression of N -methyl-D- aspartate receptor(NMDAR1)subunit splice variant mRNA is altered by developmental exposure to Pb~(2+)[J].Brain Res Mol Brain Res,2000,76:299-305.
[25]Rajat S,et al.Lipoperoxidative damage on lead exposure in rat brain and its implications on membrane bound enzymes[J].Pharmacol and Toxicol,1994,74:66-71.
[26]Shafiq-ur-Rehman S.Rehman S.Chandra O,Abdulla M.Evaluation of malondialdehyde as an index of lead damage in rat brain homogenates [J].Biometals,1995,8:275-279.
[27]Flora GJ,Seth PK.Alterations in some membrane properties in rat brain following exposure to lead[J].Cytobios,2000,103:103-109.
[28]Lagunowich LA,Stein AP,Reuhl KR.Brain biochemistry of infants and rats exposed to lead[J].Neurotoxicology,1994,15:123-132.
[29]Dey PM,Burger J,Gochfeld M,Reuhl KR.Developmental lead exposure disturbs expression of synaptic neural cell adhesion molecules in herring gull brains[J].Toxicology,2000,146(2-3):137-147.
[30]Regan CM,Neural cell adhesion molecules,neuronal development and lead toxicity[J].Neurotoxicology,1993,14(2-3):69-74.
[31]Quinn MR.The nitric oxide synthase expression of rat cortical and hippocampal neurons changes[J].Neurosci Lett,1995,196:65-68.
[32]Xu YZ,Ruan DY,Wu Y,et al.Nitric oxide effects LTP in area CA1and CA3 of hippocampus in low-level lead-exposed rat[J].Neuro-toxicol Teratol,1998,20:69-73.
[33]吴英,等.铅对大鼠海马齿状回LTP及PPF的损伤和锌的拮抗作用.中国药理学与毒理学杂志,1997,11(2):144.
[34]李连姬,等.锌、硒对铅致小鼠学习记忆功能障碍及脑脂质过氧化的保护作用.微量元素与健康研究.1998,15(3):8.
[35]陈卫平,刘世杰.铅的肾细胞毒性及锌的保护作用.卫生毒理学杂志,1995,9(2):73.
[36]Nehru B,Dua R.The effect of dietary selenium on lead neurotoxicity[J].Environ Pathol Toxicol Oncol,1997,16(1):47.
[37]李金有,刘世杰.铅致心肌细胞死亡率、自发收缩的改变与硒对其改变影响的研究.山西医学院学报,1996,27(3):161.
[38]Flora SJ,et al.Thiamine and zinc in prevention or therapy of lead intoxication [J].Int Med Res,1989,17(1):68.
[39]Winneke G.Zinc to prevent lead poisoning.CMAJ,1996,154(11):1622.
[40]Lawton LJ,Donaldson WE.Lead induced tissue fatty2acid alterations and lipid peroxidation.Biol Trace Elem Res,1991,28(2):83.
[41]Bray TM,Bettger WJ.The physiological role of zinc as an antioxidant.Free Radic Biol Med,1990,8(3):281.
[42]Hasan U.Ozcaglar,Bulent Agirdir,Oktay Dine et al Effects of Cadmium on the Hearing System,ActaOtolaryngol.2001,121(4).393-397.
[43]Dudley RE Klassen CD.Change in hepatic glutathione concentration modify cadmium-induced hepatotoxicity[J].Toxicol Appl Pharmacol,1984,72:530-538.
[44]Alexandra P,Margeli S.Metallothioneein expression during liver regeneration after partial hepatectomy in cadmium pretreated rats[J].Archives of Toxicology,1994,16(1):253-256.
[45]Toshio T,Calmodulin-dependent calcium signal Transduction[J].Pharmacol,1988,46:101.
[46]Sharma G,Nath R,GillKD.Effect of ethanol on cadmium-induced lipid perxidation ang antioxidant enzymes in rat liver[J].Biochemical Pharmacology,1991,42:9-16.
[47]申立军,周袁芬,金泰,等.镉雌激素样作用的实验研究[J].劳动医学,2001,18(2):67-68.
[48]Hussain T,Shukla GS,Chandra SV.Effects of cadmium on Superoxide dismutase and lipid peroxidation in liver and kidney of growing rats:in vivo and in vitro studies[J].Pharmacol Toxicol,1987,60(5)355.
[49]彭双清.亚硒酸钠与硒代蛋氨酸对镉在大鼠体内分布的影响[J].中国预防医学杂志,2002,12(4):255-258.
[50]史德浩.亚硒酸钠与镉中毒预防和治疗的研究[J].江苏农学院学报,1995,16(1):57-61.
[51]彭双清,刘世杰.镉对心肌细胞钙离子通道的阻滞作用及硒的保护效应[J].中华劳动卫生职业病杂志,1999,17(3):161-163.
[52]如宝,铬与人体健康.职业与健康,1995,4:6-7.
[53]汤克勇.环境中的铬与铬的生理意义.皮革科学与工程,1996,3:41-45.
[54]《三废治理与利用》编委会,三废治理与利用,冶金工业出版 社,1995,131-156
[55]邱瑾,工业废水中常见的微量元素及对人体健康的危害.杭州师范学院学报,1994,11:108-113.
[56]江勇.汞对内耳及神经系统毒性作用[J].国外医学耳鼻咽喉科分册,1998,22(3):161-163.
[57]曹玉广,镉对大鼠肝、肾中锌、铜水平的影响.中国公共卫生学报,1995(14):106-108
[58]王取南,孙美芳,魏凌珍,等.铬致大鼠肾损害与脂质过氧化的实验研究[J].Acta Universitatis Medi Cinalis Anhui,2000,35(2):114-115.
[59]YU Xiaoxing,PENG baocheng.Accumulative toxicity and effection marrowcell miceonucles rate and sperm for mation of cards[J].Journal of Hebei medical university,1997,18(3):139-141.
[60]陈琼宇,李洪,赵一波,等.六价铬对大鼠致畸作用的研究[J].Chin J Prev Med,2000,34(1):63-64.
[61]ZHU zhiliang,ZHUANG Zhixiong,HUANG Yu,et al.Effect of chromium(Ⅵ)on DNA damage in human peripheral lymphocyte[J].Practical preventive medicine,2002,9(4):339-340.
[62]Pedraza Chaverri J,Barrera D,Medina Campos ON,et al.Time coursestudy of oxidative and nitrosative stress andantioxidant enzymes in K_2Cr_2O_7-induced nephrotoxicity.BMC Nephrol,2005,6(1):4.
[63]Dayan AD,Paine AJ.Mechanisms of chromium toxicity,carcinogenicity and allergenicity:Review of the literature from 1985 to 2000.Human &Experimental Toxicol,2001,20(9):439-451.
[64]Steams DM,Courtney KD,Giangrande PH,et al.Chromium(Ⅵ)reduction by ascorbate:role of reactive intermediates in DNA damage invitro.Environ Health Perspect,1994,102(3):21-25.
[65]Bagchi D,Stohs SJ,Downs BW,et al.Cytotoxicity and oxidativemechanisms of different forms of chromium.Toxicology,2002,180(2002):5-22.
[66]Liu KJ,Shi X.In vivo reduction of chromium(Ⅵ)and its related freeradical generation.Mol Cell Biochem,2001,22(122):41-47.
[67]Fatima S,Arivarasu NA,Banday AA.Effect of potassium dichromate onrenal brush border membrane enzymes and phosphate transport in rats.Hum Exp Toxicol,2005,24 12):631-638.
[68]Dey SK,Nayak P,Roy S.Alpha2tocopherol supplementation onchromium toxicity:a study on rat liver and kidney cell membrane.JEnviron Sci(China),2003,15(3):356-359.
[69]孙应彪,朱玉真.镍、铬、钴混合物对肾毒作用机理的研究.中国公共卫生,2002,18(2):141-142.
[70]Sakamo to M et al.Pharmaco 1 Toxico 1,1996;78:193-199.
[71]Pfeil SA et al.J Clin Gastroentero 1,1999;29(1):26-30.
[72]牟颖,等.甲基汞对生物膜流动性及通透性的影响.环境与健康杂志,1996,13(3):97-99.
[73]孙志伟,等.汞元素毒性作用的研究进展[J].中国药理学与毒理学杂志,1997;11(2):125.
[74]Levesque PC,et al.Toxicol Appl Pharmacol,1992;115(1):11-20
[75]任永.国外医学医学地理分册,1994;15(1):38-39
[76]黄雯,郭连生,陈秀伍,等.肾脏病患者与听力损伤相关性的研究[J].耳鼻咽喉一头颈外科,2002,9(4):203-206.
[77]吴桂云,钟学军,胡昭.肾功能衰竭患者脑干听觉诱发电位的监测口.实用老年医学,1996,10(2):67-70.
[78]叶任高.内科学,第五版.人民卫生出版社,2002:571.
[79]宋念艺.微量元素锌与眼病[J].微量元素与健康研究.2006,23(06):73-75.
[80]章轶锋等.铜锌超氧化物歧化酶的研究进展.四川畜牧兽医,2008,01:33-35.
[81]曹丹阳.微量元素硒与心血管疾病[J].中国地方病防治杂志.2006,21(03):32-33.
[82]张红,李小利,高海青.微量元素与心血管疾病[J].国外医学.医学地理分册.2006,27(03):911.
[83]陈昭,张晶,佟冬青,刘育晖.微量元素与心血管疾病关系研究现状[J].北华大学学报(自然科学版).2003,4(03):31-33.
[84]孙德生.微量元素与身体健康.江西化工.2003,4:46-51.
[85]周静,汪会玲.微量元素与铅毒性.河北职工医学院学报,1998,19(3):31-34
[86]史德浩.亚硒酸钠与镉中毒预防和治疗的研究[J].江苏农学院学报,1995,16(1):57-61
[87]刘苹,李健,吴锡南,等.甲基汞对亲仔两代大鼠的神经行为毒性效应.环境与健康杂志,2001,18(6):339-342.
[88]Zalups RK.Molecular interactions with mercury in the kidney.Am SocPharmacol Exp Therap,2001(52)1:113-143.
[89]陈可风,冯成彬,李沛荣,等.汞性肾损伤的临床研究.中华劳动卫生职业病杂志,2002,20(3):217-218.
[90]Worth RG,Espe RM,Warra NS,et al.Mercury inhibition of neutrophilactivity:Evidence of aberrant cellular signalling and incoherent cellularmetabolism.Scand J Immunol,2001(53):49-55.
[91]Davis BJ,Price HC,O'Connor RW,et al.Nercury vapor and female productive toxicity.Toxicol Sci,2001,59:291-296.
[92]连婉芬,杜顺贵,何鸿山,等.长期低浓度汞接触工人生化免疫指标的初步观察.职业卫生与病伤,2000,15(2):78-79.
[93]Manuchehr,Abedi Valugerdi,Hu H,et al.Mercury-induced anti-nucleolar autoantibodies can transgress the membrane of living cells in vivo and in vitro.Intern Immuno,1999,11(4):605-615.
[94]林剑峰.必需微量元素锌营养研究进展.临床医药实践,2004,12:89.
[2]李红军,白忠贞,王桂敏,童振,李茂进.锌、硒单独与联合作用对镉毒性拮抗作用的研究。职业医学 1997,24(3),9-11
[3]王世俊.金属中毒.第二版,北京:人民卫生出版社,1988,215.
[4]刘爱萍,赵金垣,刘亚宁,赵新华,龙曼海.锌对急性镉中毒性肾损伤保护作用的研究.中国工业医学杂志 1999,12(3),132-135.
[5]刘爱萍,赵金垣,刘亚宁,赵新华,邵涵如,龙曼海.硒对急性镉中毒性肾损伤保护作用的研究.中国工业医学杂志 1997,10(4)193-197.
[6]Volkmar,Cook EH,Pomeroy J et al.Practice parameters for the assessment and treatment of children,adolescents,and adults with autism and other pervasive developmental disorders.J Am Acad Child Adolesc Psychiatry.1999,38:12.
[7]Gillberg C,Wing L.Autism not an extremely rare disorder(Re2 view article).Acta Psychiatry Scand,1999,99:399-400.
[8]Donaldson W.E.and Leemina T.K.Toxlcal Appl.pharmical,1984,73:119.
[9]Stacey N H,Cantilena L R,Klaassen C D,et al.Cadmium toxicity and lipid peroxidation in iso lated rat hepatocytes.Toxicol Appl Pharmacol,1980,53:470.
[10]张献清.金属中毒与脂质过氧化.工业卫生与职业病,1992,18(4):246.
[11]陈建青.锌对镉毒性的拮抗作用.国外医学卫生学分册,1990,5:279.
[12]杨成峰.硒镉相互作用的研究进展.国外医学卫生学分册,1992,2:76.
[13]Gozdzik-Zolnierkiewiez,Moszynski B.Nerve in experimental lead poisoning [J].Acta Otolaryngologoca,1969,68:85-89.
[14]Schwartz J,Otto D.Blood lead hearing thresholds and neuro behavioral development in children and youths.
[15]Schwart J,Otto D.Lead and minor hearing impairment[J].Arch Environ Health,1991,46(5):300-305.
[16]Dietrich KN,Succop PA,Berger OG,et al.Lead exposure and the central auditory processing abilities and cognitive development of urban children:the Cincinnati lead study cohortatage 5 years[J].Neuro toxicol Teratol,1992,14:51-56.
[17]Forst LS,Freels S,Persky V.Occupational lead exposure and hearing loss[J].J OEM,1997,39:658-660.
[18]Meijerman I,Blom WM,deBont HJ,et al.Analysis of differential effects of Pb~(2+)on protein kinase C isozymes[J].Toxicol Appl Pharmacol,1999,156:40-45.
[19]Cremin JD Jr,Smith DR.In vitro vs in vivo Pb effects on brain protein kinase C activity[J].Environ Res,2002,90:191-199.
[20]颜崇淮,沈晓明,吴圣楣.铅对未成熟脑神经毒性机制的研究进展[J].国外医学儿科学分册,1997,24:129-132.
[21]Bouton CM,Frelin LP,Forde CE,et al.Synaptotagmin Ⅰ is a molecular target for lead[J].J Neurochem,2001,76:1724-1735.
[22]付大干,李华强.铅对未成熟脑发育的影响及其作用机制的研究进展[J].中华劳动卫生职业病杂志,2001,19:149-151.
[23]Nihei MK,Desmond NL,McGlothan JL,et al.N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficitsof long-term potentiation and spatial learning[J].Neuroscience,2000,99:233-242.
[24]Guilarte TR,McGlothan JL,Nihei MK.Hippocampal expression of N -methyl-D- aspartate receptor(NMDAR1)subunit splice variant mRNA is altered by developmental exposure to Pb~(2+)[J].Brain Res Mol Brain Res,2000,76:299-305.
[25]Rajat S,et al.Lipoperoxidative damage on lead exposure in rat brain and its implications on membrane bound enzymes[J].Pharmacol and Toxicol,1994,74:66-71.
[26]Shafiq-ur-Rehman S.Rehman S.Chandra O,Abdulla M.Evaluation of malondialdehyde as an index of lead damage in rat brain homogenates [J].Biometals,1995,8:275-279.
[27]Flora GJ,Seth PK.Alterations in some membrane properties in rat brain following exposure to lead[J].Cytobios,2000,103:103-109.
[28]Lagunowich LA,Stein AP,Reuhl KR.Brain biochemistry of infants and rats exposed to lead[J].Neurotoxicology,1994,15:123-132.
[29]Dey PM,Burger J,Gochfeld M,Reuhl KR.Developmental lead exposure disturbs expression of synaptic neural cell adhesion molecules in herring gull brains[J].Toxicology,2000,146(2-3):137-147.
[30]Regan CM,Neural cell adhesion molecules,neuronal development and lead toxicity[J].Neurotoxicology,1993,14(2-3):69-74.
[31]Quinn MR.The nitric oxide synthase expression of rat cortical and hippocampal neurons changes[J].Neurosci Lett,1995,196:65-68.
[32]Xu YZ,Ruan DY,Wu Y,et al.Nitric oxide effects LTP in area CA1and CA3 of hippocampus in low-level lead-exposed rat[J].Neuro-toxicol Teratol,1998,20:69-73.
[33]吴英,等.铅对大鼠海马齿状回LTP及PPF的损伤和锌的拮抗作用.中国药理学与毒理学杂志,1997,11(2):144.
[34]李连姬,等.锌、硒对铅致小鼠学习记忆功能障碍及脑脂质过氧化的保护作用.微量元素与健康研究.1998,15(3):8.
[35]陈卫平,刘世杰.铅的肾细胞毒性及锌的保护作用.卫生毒理学杂志,1995,9(2):73.
[36]Nehru B,Dua R.The effect of dietary selenium on lead neurotoxicity[J].Environ Pathol Toxicol Oncol,1997,16(1):47.
[37]李金有,刘世杰.铅致心肌细胞死亡率、自发收缩的改变与硒对其改变影响的研究.山西医学院学报,1996,27(3):161.
[38]Flora SJ,et al.Thiamine and zinc in prevention or therapy of lead intoxication [J].Int Med Res,1989,17(1):68.
[39]Winneke G.Zinc to prevent lead poisoning.CMAJ,1996,154(11):1622.
[40]Lawton LJ,Donaldson WE.Lead induced tissue fatty2acid alterations and lipid peroxidation.Biol Trace Elem Res,1991,28(2):83.
[41]Bray TM,Bettger WJ.The physiological role of zinc as an antioxidant.Free Radic Biol Med,1990,8(3):281.
[42]Hasan U.Ozcaglar,Bulent Agirdir,Oktay Dine et al Effects of Cadmium on the Hearing System,ActaOtolaryngol.2001,121(4).393-397.
[43]Dudley RE Klassen CD.Change in hepatic glutathione concentration modify cadmium-induced hepatotoxicity[J].Toxicol Appl Pharmacol,1984,72:530-538.
[44]Alexandra P,Margeli S.Metallothioneein expression during liver regeneration after partial hepatectomy in cadmium pretreated rats[J].Archives of Toxicology,1994,16(1):253-256.
[45]Toshio T,Calmodulin-dependent calcium signal Transduction[J].Pharmacol,1988,46:101.
[46]Sharma G,Nath R,GillKD.Effect of ethanol on cadmium-induced lipid perxidation ang antioxidant enzymes in rat liver[J].Biochemical Pharmacology,1991,42:9-16.
[47]申立军,周袁芬,金泰,等.镉雌激素样作用的实验研究[J].劳动医学,2001,18(2):67-68.
[48]Hussain T,Shukla GS,Chandra SV.Effects of cadmium on Superoxide dismutase and lipid peroxidation in liver and kidney of growing rats:in vivo and in vitro studies[J].Pharmacol Toxicol,1987,60(5)355.
[49]彭双清.亚硒酸钠与硒代蛋氨酸对镉在大鼠体内分布的影响[J].中国预防医学杂志,2002,12(4):255-258.
[50]史德浩.亚硒酸钠与镉中毒预防和治疗的研究[J].江苏农学院学报,1995,16(1):57-61.
[51]彭双清,刘世杰.镉对心肌细胞钙离子通道的阻滞作用及硒的保护效应[J].中华劳动卫生职业病杂志,1999,17(3):161-163.
[52]如宝,铬与人体健康.职业与健康,1995,4:6-7.
[53]汤克勇.环境中的铬与铬的生理意义.皮革科学与工程,1996,3:41-45.
[54]《三废治理与利用》编委会,三废治理与利用,冶金工业出版 社,1995,131-156
[55]邱瑾,工业废水中常见的微量元素及对人体健康的危害.杭州师范学院学报,1994,11:108-113.
[56]江勇.汞对内耳及神经系统毒性作用[J].国外医学耳鼻咽喉科分册,1998,22(3):161-163.
[57]曹玉广,镉对大鼠肝、肾中锌、铜水平的影响.中国公共卫生学报,1995(14):106-108
[58]王取南,孙美芳,魏凌珍,等.铬致大鼠肾损害与脂质过氧化的实验研究[J].Acta Universitatis Medi Cinalis Anhui,2000,35(2):114-115.
[59]YU Xiaoxing,PENG baocheng.Accumulative toxicity and effection marrowcell miceonucles rate and sperm for mation of cards[J].Journal of Hebei medical university,1997,18(3):139-141.
[60]陈琼宇,李洪,赵一波,等.六价铬对大鼠致畸作用的研究[J].Chin J Prev Med,2000,34(1):63-64.
[61]ZHU zhiliang,ZHUANG Zhixiong,HUANG Yu,et al.Effect of chromium(Ⅵ)on DNA damage in human peripheral lymphocyte[J].Practical preventive medicine,2002,9(4):339-340.
[62]Pedraza Chaverri J,Barrera D,Medina Campos ON,et al.Time coursestudy of oxidative and nitrosative stress andantioxidant enzymes in K_2Cr_2O_7-induced nephrotoxicity.BMC Nephrol,2005,6(1):4.
[63]Dayan AD,Paine AJ.Mechanisms of chromium toxicity,carcinogenicity and allergenicity:Review of the literature from 1985 to 2000.Human &Experimental Toxicol,2001,20(9):439-451.
[64]Steams DM,Courtney KD,Giangrande PH,et al.Chromium(Ⅵ)reduction by ascorbate:role of reactive intermediates in DNA damage invitro.Environ Health Perspect,1994,102(3):21-25.
[65]Bagchi D,Stohs SJ,Downs BW,et al.Cytotoxicity and oxidativemechanisms of different forms of chromium.Toxicology,2002,180(2002):5-22.
[66]Liu KJ,Shi X.In vivo reduction of chromium(Ⅵ)and its related freeradical generation.Mol Cell Biochem,2001,22(122):41-47.
[67]Fatima S,Arivarasu NA,Banday AA.Effect of potassium dichromate onrenal brush border membrane enzymes and phosphate transport in rats.Hum Exp Toxicol,2005,24 12):631-638.
[68]Dey SK,Nayak P,Roy S.Alpha2tocopherol supplementation onchromium toxicity:a study on rat liver and kidney cell membrane.JEnviron Sci(China),2003,15(3):356-359.
[69]孙应彪,朱玉真.镍、铬、钴混合物对肾毒作用机理的研究.中国公共卫生,2002,18(2):141-142.
[70]Sakamo to M et al.Pharmaco 1 Toxico 1,1996;78:193-199.
[71]Pfeil SA et al.J Clin Gastroentero 1,1999;29(1):26-30.
[72]牟颖,等.甲基汞对生物膜流动性及通透性的影响.环境与健康杂志,1996,13(3):97-99.
[73]孙志伟,等.汞元素毒性作用的研究进展[J].中国药理学与毒理学杂志,1997;11(2):125.
[74]Levesque PC,et al.Toxicol Appl Pharmacol,1992;115(1):11-20
[75]任永.国外医学医学地理分册,1994;15(1):38-39
[76]黄雯,郭连生,陈秀伍,等.肾脏病患者与听力损伤相关性的研究[J].耳鼻咽喉一头颈外科,2002,9(4):203-206.
[77]吴桂云,钟学军,胡昭.肾功能衰竭患者脑干听觉诱发电位的监测口.实用老年医学,1996,10(2):67-70.
[78]叶任高.内科学,第五版.人民卫生出版社,2002:571.
[79]宋念艺.微量元素锌与眼病[J].微量元素与健康研究.2006,23(06):73-75.
[80]章轶锋等.铜锌超氧化物歧化酶的研究进展.四川畜牧兽医,2008,01:33-35.
[81]曹丹阳.微量元素硒与心血管疾病[J].中国地方病防治杂志.2006,21(03):32-33.
[82]张红,李小利,高海青.微量元素与心血管疾病[J].国外医学.医学地理分册.2006,27(03):911.
[83]陈昭,张晶,佟冬青,刘育晖.微量元素与心血管疾病关系研究现状[J].北华大学学报(自然科学版).2003,4(03):31-33.
[84]孙德生.微量元素与身体健康.江西化工.2003,4:46-51.
[85]周静,汪会玲.微量元素与铅毒性.河北职工医学院学报,1998,19(3):31-34
[86]史德浩.亚硒酸钠与镉中毒预防和治疗的研究[J].江苏农学院学报,1995,16(1):57-61
[87]刘苹,李健,吴锡南,等.甲基汞对亲仔两代大鼠的神经行为毒性效应.环境与健康杂志,2001,18(6):339-342.
[88]Zalups RK.Molecular interactions with mercury in the kidney.Am SocPharmacol Exp Therap,2001(52)1:113-143.
[89]陈可风,冯成彬,李沛荣,等.汞性肾损伤的临床研究.中华劳动卫生职业病杂志,2002,20(3):217-218.
[90]Worth RG,Espe RM,Warra NS,et al.Mercury inhibition of neutrophilactivity:Evidence of aberrant cellular signalling and incoherent cellularmetabolism.Scand J Immunol,2001(53):49-55.
[91]Davis BJ,Price HC,O'Connor RW,et al.Nercury vapor and female productive toxicity.Toxicol Sci,2001,59:291-296.
[92]连婉芬,杜顺贵,何鸿山,等.长期低浓度汞接触工人生化免疫指标的初步观察.职业卫生与病伤,2000,15(2):78-79.
[93]Manuchehr,Abedi Valugerdi,Hu H,et al.Mercury-induced anti-nucleolar autoantibodies can transgress the membrane of living cells in vivo and in vitro.Intern Immuno,1999,11(4):605-615.
[94]林剑峰.必需微量元素锌营养研究进展.临床医药实践,2004,12:89.