摘要
目的探讨α-硫辛酸(α-LA)对甲基汞所致大鼠脑氧化损伤的影响。方法实验用Wistar大鼠40只,雌雄各半,每组10只,按体重随机分为4组。分别为对照组,低、高甲基汞染毒组和α-LA预处理组。对照组和低、高甲基汞染毒组先以0.9%氯化钠溶液皮下注射,α-LA预处理组皮下注射35μmol/kgα-LA;2 h后,对照组腹腔注射0.9%氯化钠溶液,低、高甲基汞染毒组和α-LA预处理组腹腔注射甲基汞4、12、12μmol/kg,染毒容量为5 ml/kg;干预隔日1次,每周3次,染毒每日1次,每周5次,连续干预与染毒4周。最后一次染毒24 h后,在每组大鼠中随机抽取6只,用水合氯醛腹腔注射麻醉,心脏放血,解剖取脑,在冰浴下迅速分离大脑皮质,制备10%的组织匀浆,测定大脑皮质Hg含量、MDA含量,蛋白巯基、羰基含量及SOD、GSH-Px活力;每组中其余4只大鼠,用水合氯醛麻醉,左心室灌流固定后,解剖取脑,在冰浴下迅速分离大脑皮质,应用多聚甲醛固定,免疫组化法测定8-OHdG含量,HE染色进行病理学观察。结果随着染甲基汞剂量的升高,大鼠脑汞、MDA、蛋白羰基含量及8-OHdG含量阳性面积比、积分光密度值均升高,蛋白巯基含量及SOD及GSH-Px活力明显降低,HE染色病理损伤加重;与单纯染高剂量甲基汞组比较,α-LA干预组大鼠脑汞含量差异不显著,MDA、蛋白羰基含量及8-OHdG含量阳性面积比、积分光密度值均降低,蛋白巯基含量、SOD及GSH-Px活力均升高,HE染色病理损伤有所恢复;差异有统计学意义(P<0.05或P<0.01)。结论α-LA预处理对甲基汞所致大鼠脑氧化损伤有一定的拮抗作用。
Objective To observe the protective effect of alpha-lipoic acid（α-LA）on the oxidative damage of brain caused by methylmercury in rats.Methods 40 wistar rats were randomly divided into 4 groups by weight,10 rats in each group,the first was control group,the second and third were low-and high-dose methylmercury groups,the fourth was α-LA pretreated group of α-LA.The rats in first,second and third groups were subcutaneous injected with 0.9% NaCl,the rats in fourth group were injected 35 μmol/kg α-LA;2 hours later,rats of first group were peritoneally injected with 0.9% NaCl,rats of second group were peritoneally injected with 4 μmol/kg CH3HgCl,rats of third and fourth groups were peritoneally injected with 12 μmol/kg CH3HgCl.The α-LA pretreatment was given in 2 days interval,3 times a week,while methyl mercury was given everyday,5 times a week,all lasted for 4 weeks.24 hours after last injection of methylmercury,6 rats in each groups were killed,taking the brains and separating the cerebral cortex on ice bath,then prepare 10% homegenate,determine the contents of Hg,MDA,protein sulfydryl,protein carbonyl in it,and the activities of SOD and GSH-Px in the homogenate.Another 4 rats remained in each group were made left ventricular perfusion with paraformaldehyde,and rapidly separated the cerebral cortex on ice bath for the determination of 8-OHdG content（by immunohistochemistry method）and the pathological examination.Results The results showed that compared with control group,the contents of mercury,MDA,protein carbonyl were all obviously increased（P0.01）,the levels of protein sulfydryl,SOD and GSH-Px were all significantly reduced（P0.01）,the 8-OHdG positive area ratio and integral light density in brain were also clearly increased too,with the exposed dose of mercury（P0.01）.While the indices mentioned above in α-LA pretreated group were all improved compared with 12 μmol/kg mercury group（P0.01 or P0.05）.Conclusion Methylmercury can induced oxidative damage in brain of rats,while α-LA has a certain protective effect on this kind of damage.
出处
《中国工业医学杂志》
CAS
北大核心
2013年第3期167-170,173,F0003,共6页
Chinese Journal of Industrial Medicine
基金
国家自然科学基金资助项目(编号:81172631)
关键词
甲基汞
α-LA
氧化损伤
methylmercury
alpha-lipoic acid（α-LA）
oxidative damage
