文献类型：期刊文献

中文题名：钙蛋白酶抑制剂Ⅲ MDL 28170对大鼠甲基汞急性神经毒性的拮抗作用

英文题名：Antagonistic effect of calpain inhibitor MDL 28170 on acute methylmercury neurotoxicity in rats

作者：张剑[1];张敏[2]

机构：[1]绍兴文理学院医学院药理研究室;[2]绍兴文理学院附属医院

年份：2010

期号：1

起止页码：44

中文期刊名：中国药理学与毒理学杂志

外文期刊名：Chinese Journal of Pharmacology and Toxicology

收录：CSTPCD、、Scopus、CSCD2011_2012、北大核心2008、北大核心、CSCD

基金：国家自然科学基金资助项目(30800360);浙江省自然科学基金资助项目(Y204364)~~

语种：中文

中文关键词：MDL;28170;蛋白酶抑制剂;甲基汞;神经元;细胞凋亡

外文关键词：MDL 28170 protease inhibitors methylmercury neurons apoptosis

中文摘要：目的为寻找治疗甲基汞急性中毒作用药物新靶点,探讨钙蛋白酶抑制剂ⅢMDL28170对甲基汞急性神经毒性的拮抗作用。方法大鼠随机分为正常对照组、MDL28170(50mg.kg-1,ip)对照组、甲基汞(10mg.kg-1,ig)中毒模型组与MDL28170干预组(同时ig甲基汞和ip MDL28170)。Morris水迷宫检测大鼠学习记忆能力,免疫组织化学法观察脑μ-钙蛋白酶免疫阳性神经元,Western蛋白印迹法检测脑μ-钙蛋白酶表达,TUNEL法观察脑神经元凋亡,免疫荧光染色法观察脑皮质神经元微管相关蛋白2(MAP2)含量。结果大鼠ig给予甲基汞3或7d,中毒模型组出现神经系统损害行为学表现,水迷宫逃避潜伏期明显延长(P<0.01);脑皮质神经元内μ-钙蛋白酶的表达和活性明显升高(P<0.01);脑皮质神经元凋亡显著增加(P<0.01);神经元MAP2含量明显降低。同时给予MDL28170可明显减轻上述改变。结论μ-钙蛋白酶可能参与甲基汞中毒导致的神经细胞凋亡。MDL28170可明显抑制甲基汞的神经毒性损害,可能对甲基汞中毒具有治疗作用。

外文摘要：OBJECTIVE To explore the antagonistic effect of calpain inhibitor Ⅲ MDL 28170 on acute methylmercury（MeHg） neurotoxicity.METHODS The rats were randomly divided into MDL 28170（50 mg·kg^-1,ip） control group,MeHg（10 mg·kg^-1,ig）,and MeHg（10 mg·kg^-1,ig）＋MDL 28170（50 mg·kg^-1,ip） group.The escape latencies were observed by Morris water maze test.The neurons of positive μ-calpain were determined by immunohistochemical method,the expression of μ-calpain was analyzed by Western blotting,apoptotic neurons were observed by TUNEL method,and microtubule-associated protein 2（MAP2） expression was detected in neuron by immunohistochemical method.RESULTS MeHg was ig given for 3-7 d,the initial signs of behavioral changes developed in MeHg group,the escape latencies were lengthened in Morris water maze test（P〈0.01）.The expression and activity of μ-calpain elevated obviously in parietal cerebral neurons（P〈0.01）,neuronal apoptosis was markedly increased（P〈0.01）,and the decomposition of MAP2 was reduced in cortical neurons obviously.And the above changes were suppressed obviously by treatment of MDL 28170.CONCLUSION μ-Calpain may correlate with neuronal apoptosis induced by MeHg,MDL 28170 markedly reduces neuronal apoptosis,which might act as therapeutical method for MeHg poison.