利用自由基清除剂依达拉奉研究自由基在1，2-二氯乙烷（1，2-DCE）致脑水肿过程中的作用
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摘要
[目的]探讨自由基在1,2-DCE引起脑水肿过程中的作用,为1,2-DCE急性中毒的预防,诊断,治疗提供依据。[方法]复制大鼠1,2-DCE脑水肿模型,并在染毒过程中和染毒后分别腹腔注射自由基清除剂依达拉奉。制作组织切片和电镜切片,并检测各组动物脑组织干湿重的变化以及SOD、MDA、GSH含量的改变,并研究自由基检测的结果与1,2-DCE导致脑水肿之间的关系;同时通过混合培养神经元细胞和神经胶质细胞,然后用1,2-DCE进行分剂量染毒和分时间梯度染毒,通过对染毒后细胞的SOD、MDA含量的检测,进一步探讨自由基在1,2-DCE导致脑水肿过程中的作用机制。[结果]在脑组织干湿重比较中,染毒组与其余各组相比,脑组织含水量有明显增多,而染毒+干预组脑组织含水量较染毒组有所降低;随着染毒组中自由基清除剂的剂量增加,SOD、GSH活力逐渐上升,而MDA含量逐渐降低;通过细胞培养发现:用1,2-DCE染毒混合培养的神经元细胞和神经胶质细胞时,细胞出现相应损伤的形态学变化,SOD活力随着自由基清除剂的剂量加大而逐渐上升,MDA随着自由基清除剂的剂量加大而逐渐降低。[结论]由于自由基清除剂-依达拉奉的加入,使得体内大鼠模型和体外培养的神经细胞的氧化损伤都降低了,这说明在1,2-DCE导致脑水肿的过程中,自由基起着很重要的作用。
[Objective]To explore the effect of 1,2-DCE in brain edema process and provide theoretical foundation for the prevention,diagnosis and treatment for acute intoxication of 1,2-DCE.[Method]The main measurements have two parts:in vitro and in vivo.In the first part we established the mouse brain edema model induced by 1,2-DCE and then peritoneal inject edaravone(free radical scavenger)followed treatment of 1,2-DCE.After the tissue section and electron microscopic section were made,we investigated the relationship between SOD,MDA,GSH concentration and brain edema.The second part,we treated cortical neuron with different levels of 1,2-DCE at different time and then the SOD,MDA、GSH activities were detected to discuss the mechanism of brain edema induced by 1,2-DCE.[Result]In the comparison of brain weight between different groups we found that 1,2-DCE treated mouse contains much more water in brain than groups added free radical scavenger.In other groups we found the activity of SOD, GSH rised and MDA dropped with the increasing of scavenger concentration.In cell culture, besides cell morphology diversity we also found the similar activity change in SOD,GSH and MDA.[Conclusion]According to the fact that the addition of edaravone,a kind of free radical scavenger,significantly depressed the oxidative damage induced by 1,2-DCE,free radical plays an important role in the brain edema process induced by the 1,2-DCE.
[Objective]To explore the effect of 1,2-DCE in brain edema process and provide theoretical foundation for the prevention,diagnosis and treatment for acute intoxication of 1,2-DCE.[Method]The main measurements have two parts:in vitro and in vivo.In the first part we established the mouse brain edema model induced by 1,2-DCE and then peritoneal inject edaravone(free radical scavenger)followed treatment of 1,2-DCE.After the tissue section and electron microscopic section were made,we investigated the relationship between SOD,MDA,GSH concentration and brain edema.The second part,we treated cortical neuron with different levels of 1,2-DCE at different time and then the SOD,MDA、GSH activities were detected to discuss the mechanism of brain edema induced by 1,2-DCE.[Result]In the comparison of brain weight between different groups we found that 1,2-DCE treated mouse contains much more water in brain than groups added free radical scavenger.In other groups we found the activity of SOD, GSH rised and MDA dropped with the increasing of scavenger concentration.In cell culture, besides cell morphology diversity we also found the similar activity change in SOD,GSH and MDA.[Conclusion]According to the fact that the addition of edaravone,a kind of free radical scavenger,significantly depressed the oxidative damage induced by 1,2-DCE,free radical plays an important role in the brain edema process induced by the 1,2-DCE.
引文
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[3]刘卫平.脑水肿自由基病理机制研究进展.国外医学神经病学.神经外科学分册1994,21(1):3-6
[4]张勤丽,王林平,郭小丽,等.1,2-二氯乙烷对血脑屏障的损伤作用.中华劳动卫生职业病杂志,2006,24(4):239-243
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[2]李来玉,黄建勋,陈润涛,等.1,2-二氯乙烷的吸入毒性研究卫生毒理学杂志,1996,10(3):211
[3]叶伟.1,2-二氯乙烷的急性毒性及职业中毒.工业卫生与职业病,1998,14(2):144
[4]常元勋.1,2-二氯乙烷的毒理学进展.国外医学卫生学分册,1983,(6):329
[5]李来玉,黄建勋,彭兴平,等.1,2-二氯乙烷吸入致大鼠中枢神经系统损伤的病理改变.卫生毒理学杂志,1996,10(3):194
[6]黄建勋,牛侨,梁友信,等.1,2-二氯乙烷致脑水肿过程中自由基的作用研究.中国职业医学,2002,29(4):2-6
[7]刘卫平.脑水肿自由基病理机制研究进展.国外医学神经病学神经外科学分册1994,21(1):3-6
[8]范乐明.脑水肿发病机理研究的某些进展.江苏医药,1986,(10):543-545
[9]Tanaka M.Pharmacological and clinical profile of the free radical scavenger edaravone as a neuroprotective agent.Nippon Yakurigaku Zasshi,2002,119:301-308
[10]Tabrizchi R.Edaravone Mitsubishi-Tokyo.Curr Opin Investig Drugs,2000,1:347-354
[11]Watanabe T,Morita I,Nishi H,et al.Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro.Prostaglandins Leukot Essent Fatty Acids,1988,33:81-87
[12]Ochi H,Morita I,Murota S,et al.Mechanism for endothelial cell injury induced by 15-hydroperoxyeicosatetraenoic acid,an archidonate lipoxygenase product.Biochem Biophys Acta,1992,1136:247-252
[13]Nishi H,Watanabe T,Sakurai H,et al.Effect of MCI-186 on brain edema in rats.Stroke,1989,20:1236-1240
[14]Minhaz U,Tanaka M,Tsukamoto H,et al.Effect of MCI-186 on postischemic reperfusion injury in isolated rat heart.Free Radic Res,1996,24:361-367
[15]Okatani Y,Wakatsuki A,Enzan H,et al.Edaravone protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat liver.Eur J Pharmacol 2003,465:163-170
[16]Kono H,Asakawa M,Fujii H,et al.Edaravone,a novel free radical scavenger,prevents liver injury and mortality in rats administered endotoxin.J Pharmacol Exp Ther 2003,307:74-82
[17]Tomatsuri N,Yoshida N,Takagi T,et al.Edaravone,a newly developed radical scavenger,protects against ischemia-reperfusion injury of the small intestine in rats.Int J Mol Med,2004,13:105-109
[18]蒋轶文,刘书丽,李丽,等.重度二氯乙烷中毒致中毒性脑病的治疗.中华劳动卫生职业病杂志,2006,24(8):506-507
[19]李来玉.二氯乙烷中毒性脑损伤.中国药理学与毒理学杂志,1997,11(2):152
[20]何风生.急性中毒性脑水肿的发病机理.中国工业医学杂志,1989,2(3):40
[21]欧阳宗仁.急性脑水肿的发病机理.实用内科学杂志,1984,4(4):170-171
[22]Nakajima Y,Masaoka N,Hayayawa Y,et al.The Production of Hydroxyl Radicals in the Fetal Lamb Brain Resulting from Occlusion of the Umbilical Circulation and the Transplacental Effect of MCI-186 to Inhibit Hydroxyl Radical Production.Pediatric Research,59(2):216-220
[23]A.Novelli,J.A.Reilly,P.G.Lysko,et al.Glutamate becomes neurotoxic via the NMDA receptor when intracellular energy levels are reduced.Brain Res,1988,451:205-212.
[24]Kaufmann JA,Bickford PC,Taglialatela G.Free radical-dependent changes in constitutive Nuclear factor kappa B in the aged hippocampus.Neuroreport,2002,13(15):1917-1928
[25]陈志宏,齐聪儒,杨松鹤,等.器官衰老和自由基学说.承德医学院学报,2003,20(2):143-145
[26]Nystrom T.The free-radical hypothesis of aging goes prok aryotic.Cellular and molecular life sciences:CMLS,2003,60(7):1333-1341
[27]赵克然,杨毅军,曹道俊.氧自由基与临床.北京:中国医药出版社,2002:14-70
[28]Watanabe T,Yuki S,Egawa M,Nishi H:Protective effects of MCI-186 on cerebral ischemia:possible involvement of free radical scavenging and antioxidant actions.J Pharmacol Exp Ther,1994,268:1597-1604
[29]Abe K,Yuki S,Kogure K.Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.Stroke,1988,19:480-485
[30]Nishi H,Watanabe T,Sakurai H,et al.Effect of MCI-186 on brain edema in rats.Stroke,1989,20:1236-1240
[1]何风生.急性中毒性脑水肿的发病机理.中国工业医学杂志,1989,2(3):40
[2]范乐明.脑水肿发病机理研究的某些进展.江苏医药,1986,(10):543-545
[3]刘卫平.脑水肿自由基病理机制研究进展.国外医学神经病学.神经外科学分册1994,21(1):3-6
[4]张勤丽,王林平,郭小丽,等.1,2-二氯乙烷对血脑屏障的损伤作用.中华劳动卫生职业病杂志,2006,24(4):239-243
[5]娄小华,徐钱,王黎明,等.甲醛吸入致小鼠脑和肾组织的氧化损伤作用研究.公共卫生与预防医学,2006(17)1:10-3
[6]欧阳宗仁.急性脑水肿的发病机理.实用内科学杂志,1984,4(4):170-171
[7]于明琨,朱诚,张光霁.急性颅脑损伤组织氨基酸含量变化及意义.中华神经外科杂志,1994,10:34-37
[8]Miller Lp,Lyeth BG,Jenkins LM,et al.Excitatory amino acid receptor subtype binding following traumatic brain injury.Brain Res,1990,526:103-107
[9]Feeney DM,Weisend MP,Linn W J,et al.Responses to cortical injury:Methodology and local effects of contusion in the rat.Brain Res,1981,211:67-77
[10]刘永学,吕宝璋.小鼠大脑皮质N-甲基-D-天门冬氨酸受体的鉴定及其在衰老时的变化.中华应用生理学杂志,1994,11:347
[11]于明琨,朱诚,张光霁,等.急性脑损伤后猫突触膜N-甲基D-天门冬氨酸受体的变化.中华神经外科杂志,1995,11:347
[12]徐如祥,易声禹,吴声伶,等.神经细胞Ca~(2+)通道变化对鼠血脑屏障和外伤性脑水肿的影响.中华神经外科杂志,1992,8:41-44
[13]罗成义,王清华,徐如祥.大鼠大脑损伤后皮质NMDA受体活性变化与脑水肿的关系,中华创伤杂志,1998,14(4):203-205
[14]罗成义,徐如祥.脑损伤后谷氨酸含量变化与脑水肿的关系.广东医学,1999,20(2):88-89
[15]王克万,杨志焕,王正国,等.培养大鼠脑皮层神经元损伤后C-fos蛋白表达.中华创伤杂志,1998,14(4):219-222
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