长期饮酒对小鼠性腺及免疫器官的影响
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摘要
我国是酒饮料生产消费大国,酒中含的主要成分为乙醇。少量饮酒对身体有益和大量酗酒对身体有害是大家公认的。过量饮酒产生多种疾病,对人类的健康危害日趋严重,尤其在欧美国家,慢性酒精中毒的发病率仅次于心脑血管和癌症,占第三位。
大量研究表明长期饮酒与包括生殖系统和免疫系统在内的机体多系统的疾病密切相关。乙醇对性腺有毒性作用,干扰体内卵子发生,影响雌性动物的发情周期,同时酒精可以损害卵巢,使卵巢激素分泌异常,导致不排卵或无月经；Kawase等发现生精细胞在乙醇以及其代谢产物以及脂质过氧化物的直接作用下,曲细精管变性、退化、钙化,因而使精子发生减少、精子畸形、活动精子减少；也有研究表明乙醇慢性中毒直接破坏免疫系统,导致机体免疫低下和自身免疫疾病。
然而酒精对哺乳动物生殖机能的确切机制仍值得进一步探讨；另外关于酒精对哺乳动物卵巢eCG反应性的影响,目前还没有相关的研究报道；同时国内关于长期饮酒与动物机体免疫功能影响的研究还较少,有待于我们去进一步研究。
因此,我们以未成熟(KM)小鼠为实验动物模型,来探讨长期饮酒对哺乳动物性腺和免疫器官生长发育的影响。
试验选用21日龄断奶未成熟(KM)小鼠,随机分为3组,试验组Ⅰ自由饮用啤酒(含体积分数为2.8%的乙醇),试验组Ⅱ饮用稀释的白酒(含体积分数为5%的乙醇),对照组饮用自来水。试验期间定期测量体重；试验5周后对体重、脏器重等指标进行称量；同时对肝脏、脾脏和胸腺的组织学形态进行观察。(雄性)对附睾中精子密度、精子畸形率等进行检测,对睾丸的组织学形态进行观察。(雌性)试验期间检查阴道开张日龄；每组分别取4只(KM)小鼠用乙醚麻醉后测定体重、卵巢、子宫等指标；同时观察卵巢和肝脏的组织学形态；剩余12只小鼠用孕马血清促性腺激素(ecG)处理,48 h后进行麻醉、称重和组织学观察。
实验结果表明：整个试验期啤酒组体重显著增加；脾脏和胸腺重受到不同程度的影响；脾脏组织学观察发现不同程度的病变,而胸腺没有发现明显的组织学变化；肝脏重量与形态学的观察也发现了毒性作用.(雄性)精子密度显著降低,同时精子畸形率明显升高.睾丸间质间隙增宽,生精小管内生精细胞排列紊乱疏松,生精细胞间出现空隙,有的甚至变性、坏死、脱落,生精小管管壁萎缩变薄。(雌性)啤酒组和白酒组小鼠阴道开张日龄显著推迟；ecG处理前啤酒组和白酒组小鼠卵巢和子宫质量与对照组相比显著增加；ecG处理后啤酒组卵巢质量与对照组相似,但白酒组卵巢质量显著低于对照组和啤酒组,子宫与卵巢呈相似的变化；在肝脏组织形态学上也体现出了酒精的毒性作用。
由此可见,长期饮酒对小鼠的免疫功能和肝脏均有直接的毒害作用。同时也抑制了小鼠卵巢功能和睾丸功能,并且卵巢对ecG反应性显著降低,表明慢性饮酒对性腺和肝脏均有直接的毒害作用。
China is a big country of alcohol production and consumption. Ethanol is the active ingredient in alcoholic drinks. Studies have found that moderate alcohol consumption has health benefits for some people, on the other hand, medium and high consumption of alcohol harm for health, associating to many diseases such as heart attack and pancreatic canner, especially in west countries. In those countries, the death rate of chronic alcoholism ranks third, only after angiocardiopathy and cancer.
Many reports indicated that chronic ethanol is closely related to many systems diseases; include reproductive system and immune system. Lots studies indicated that the toxicity of alcohol in gonad interfere oogenesis and estrus cycle in female, and damage ovary which lead parasecretion of ovarian hormone which induce anovulation and amenorrhea. Kawase discovered that on account of the direct damage of alcohol, its metabolites and lipid peroxide to spermatogenic cell, seminiferous tubule gradually become degeneration, degradation, calcification, and then reduce spermatogenesis, sperm malformation, motile sperm decreased. There is also some studies show that chronic alcoholism destroys the immune system directly, cause low immunity and autoimmune diseases.
The actual mechanism of chronic ethanol intake on reproductive functions is worthy to be discussed further. Furthermore there is not report about the response of alcohol to equine chorionic gonadotropin (eCG). Meanwhile there are little researches about effects of chronic ethanol intake on the immunological function in animal.
Therefore, immature (KM) mice was choosed as animal model to discuss the effect of chronic ethanol on gonads and the development of immune organs of (KM)mice, which is also the primary purpose of the experiment.
Immature (KM) mice of 21 day-old were randomly allotted into three groups. GroupⅠwere fed with beer (2.8%) and GroupⅡwith diluted alcohol (5%); while the third group with fresh water was used as control. Body weight was examined periodically during the experiment.5 weeks latter, weigh the body weight and viscera weight each animal. At one time, perform histological examination of liver, spleen, thymus and testicle. What's more, sperm density and sperm abnormal rate in the epididymis were examined as well as testis histology after 5 weeks experimental treatment. The female vaginal opening age was noted during the experimental period. Four (KM) mice from each group were anatomized. Body weight, ovary, uterus and liver of each animal were measured after anesthesia with aether as well as the ovary and liver histology. Furthermore, other 12 (KM) mice were treated with ECG, and then anatomized, weighed and examined histological 48 hr later.
The results indicated that body weight of GroupⅠincreased significantly; spleen and thymus weight were affected in different degrees. There were some different degree pathological changes in the spleen histology, but no changes in thymus. The observation of liver weight and histology also suggested pathological changes in groupⅠandⅡ. In GroupⅡ, sperm concentrations in epididymis decreased significantly and sperm abnormal rates increased significantly. The intra-testis interstice in GroupⅠincreased with leydig cells hyperplasia, while the intra-testis interstice in GroupⅡincreased with leydig cells hyperplasia more than that presented in GroupⅠ. Furthermore, in GroupⅡ, the arrangement of spermatogenic cells in somniferous tubules displayed disorganized, interstice appeared among spermatogenic cells, some spermatogenic cells even became denaturalization, necrotic and fallen off. And the wall of somniferous tubules became thinner. The results indicated that the day of vaginal opening was delayed significantly in GroupⅠandⅡ. The weight of ovary and uterus in GroupⅠandⅡwere heavier than those in Control before eCG treatment. After eCG treatment, ovarian weight in Control and GroupⅠsignificantly increased, while ovarian weights in GroupⅡkept unchanged and were significantly lighter than that in Control and GroupⅠ. The observation of liver histology indicated also pathological changes in GroupⅠandⅡ.
Together, implying the directly toxic effects of chronic ethanol on the immune functions and liver functions in the mice. Chronic ethanol intake has toxic effects on mammalian development and testis functions. Chronic ethanol intake represses ovarian functions and testis functions in the mice, and depresses the response of eCG, implying the directly toxic effects of chronic ethanol on gonads and liver.
大量研究表明长期饮酒与包括生殖系统和免疫系统在内的机体多系统的疾病密切相关。乙醇对性腺有毒性作用,干扰体内卵子发生,影响雌性动物的发情周期,同时酒精可以损害卵巢,使卵巢激素分泌异常,导致不排卵或无月经；Kawase等发现生精细胞在乙醇以及其代谢产物以及脂质过氧化物的直接作用下,曲细精管变性、退化、钙化,因而使精子发生减少、精子畸形、活动精子减少；也有研究表明乙醇慢性中毒直接破坏免疫系统,导致机体免疫低下和自身免疫疾病。
然而酒精对哺乳动物生殖机能的确切机制仍值得进一步探讨；另外关于酒精对哺乳动物卵巢eCG反应性的影响,目前还没有相关的研究报道；同时国内关于长期饮酒与动物机体免疫功能影响的研究还较少,有待于我们去进一步研究。
因此,我们以未成熟(KM)小鼠为实验动物模型,来探讨长期饮酒对哺乳动物性腺和免疫器官生长发育的影响。
试验选用21日龄断奶未成熟(KM)小鼠,随机分为3组,试验组Ⅰ自由饮用啤酒(含体积分数为2.8%的乙醇),试验组Ⅱ饮用稀释的白酒(含体积分数为5%的乙醇),对照组饮用自来水。试验期间定期测量体重；试验5周后对体重、脏器重等指标进行称量；同时对肝脏、脾脏和胸腺的组织学形态进行观察。(雄性)对附睾中精子密度、精子畸形率等进行检测,对睾丸的组织学形态进行观察。(雌性)试验期间检查阴道开张日龄；每组分别取4只(KM)小鼠用乙醚麻醉后测定体重、卵巢、子宫等指标；同时观察卵巢和肝脏的组织学形态；剩余12只小鼠用孕马血清促性腺激素(ecG)处理,48 h后进行麻醉、称重和组织学观察。
实验结果表明：整个试验期啤酒组体重显著增加；脾脏和胸腺重受到不同程度的影响；脾脏组织学观察发现不同程度的病变,而胸腺没有发现明显的组织学变化；肝脏重量与形态学的观察也发现了毒性作用.(雄性)精子密度显著降低,同时精子畸形率明显升高.睾丸间质间隙增宽,生精小管内生精细胞排列紊乱疏松,生精细胞间出现空隙,有的甚至变性、坏死、脱落,生精小管管壁萎缩变薄。(雌性)啤酒组和白酒组小鼠阴道开张日龄显著推迟；ecG处理前啤酒组和白酒组小鼠卵巢和子宫质量与对照组相比显著增加；ecG处理后啤酒组卵巢质量与对照组相似,但白酒组卵巢质量显著低于对照组和啤酒组,子宫与卵巢呈相似的变化；在肝脏组织形态学上也体现出了酒精的毒性作用。
由此可见,长期饮酒对小鼠的免疫功能和肝脏均有直接的毒害作用。同时也抑制了小鼠卵巢功能和睾丸功能,并且卵巢对ecG反应性显著降低,表明慢性饮酒对性腺和肝脏均有直接的毒害作用。
China is a big country of alcohol production and consumption. Ethanol is the active ingredient in alcoholic drinks. Studies have found that moderate alcohol consumption has health benefits for some people, on the other hand, medium and high consumption of alcohol harm for health, associating to many diseases such as heart attack and pancreatic canner, especially in west countries. In those countries, the death rate of chronic alcoholism ranks third, only after angiocardiopathy and cancer.
Many reports indicated that chronic ethanol is closely related to many systems diseases; include reproductive system and immune system. Lots studies indicated that the toxicity of alcohol in gonad interfere oogenesis and estrus cycle in female, and damage ovary which lead parasecretion of ovarian hormone which induce anovulation and amenorrhea. Kawase discovered that on account of the direct damage of alcohol, its metabolites and lipid peroxide to spermatogenic cell, seminiferous tubule gradually become degeneration, degradation, calcification, and then reduce spermatogenesis, sperm malformation, motile sperm decreased. There is also some studies show that chronic alcoholism destroys the immune system directly, cause low immunity and autoimmune diseases.
The actual mechanism of chronic ethanol intake on reproductive functions is worthy to be discussed further. Furthermore there is not report about the response of alcohol to equine chorionic gonadotropin (eCG). Meanwhile there are little researches about effects of chronic ethanol intake on the immunological function in animal.
Therefore, immature (KM) mice was choosed as animal model to discuss the effect of chronic ethanol on gonads and the development of immune organs of (KM)mice, which is also the primary purpose of the experiment.
Immature (KM) mice of 21 day-old were randomly allotted into three groups. GroupⅠwere fed with beer (2.8%) and GroupⅡwith diluted alcohol (5%); while the third group with fresh water was used as control. Body weight was examined periodically during the experiment.5 weeks latter, weigh the body weight and viscera weight each animal. At one time, perform histological examination of liver, spleen, thymus and testicle. What's more, sperm density and sperm abnormal rate in the epididymis were examined as well as testis histology after 5 weeks experimental treatment. The female vaginal opening age was noted during the experimental period. Four (KM) mice from each group were anatomized. Body weight, ovary, uterus and liver of each animal were measured after anesthesia with aether as well as the ovary and liver histology. Furthermore, other 12 (KM) mice were treated with ECG, and then anatomized, weighed and examined histological 48 hr later.
The results indicated that body weight of GroupⅠincreased significantly; spleen and thymus weight were affected in different degrees. There were some different degree pathological changes in the spleen histology, but no changes in thymus. The observation of liver weight and histology also suggested pathological changes in groupⅠandⅡ. In GroupⅡ, sperm concentrations in epididymis decreased significantly and sperm abnormal rates increased significantly. The intra-testis interstice in GroupⅠincreased with leydig cells hyperplasia, while the intra-testis interstice in GroupⅡincreased with leydig cells hyperplasia more than that presented in GroupⅠ. Furthermore, in GroupⅡ, the arrangement of spermatogenic cells in somniferous tubules displayed disorganized, interstice appeared among spermatogenic cells, some spermatogenic cells even became denaturalization, necrotic and fallen off. And the wall of somniferous tubules became thinner. The results indicated that the day of vaginal opening was delayed significantly in GroupⅠandⅡ. The weight of ovary and uterus in GroupⅠandⅡwere heavier than those in Control before eCG treatment. After eCG treatment, ovarian weight in Control and GroupⅠsignificantly increased, while ovarian weights in GroupⅡkept unchanged and were significantly lighter than that in Control and GroupⅠ. The observation of liver histology indicated also pathological changes in GroupⅠandⅡ.
Together, implying the directly toxic effects of chronic ethanol on the immune functions and liver functions in the mice. Chronic ethanol intake has toxic effects on mammalian development and testis functions. Chronic ethanol intake represses ovarian functions and testis functions in the mice, and depresses the response of eCG, implying the directly toxic effects of chronic ethanol on gonads and liver.
引文
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