中文摘要：

目的探讨甲基汞急性暴露诱导大鼠不同脑区内质网应激的时间-效应关系。方法42只SD大鼠随机分为7组,染毒组腹腔注射氯化甲基汞（4mg/kg）,并在0.5、1、3、6、12和24h后麻醉断头处死。对照组腹腔注射同等剂量的生理盐水后立刻断头处死,迅速在冰上分离小脑、大脑皮层、脑干、海马和纹状体5个脑区。以蛋白印迹法测定各个脑区内质网应激的标志性蛋白Grp78的表达。同时测定大脑皮层内还原型谷胱甘肽（GSH）含量。结果甲基汞染毒后,各个脑区Grp78蛋白的表达显示了较为一致的先升高后降低的变化趋势,0.5h开始升高,6h或12h达到高峰,然后下降,24h时接近对照组水平,其中大脑皮层与脑干Grp78的变化与对照组相比分别具有统计学意义。大脑皮层Grp78蛋白的表达在染毒6h时处在最高峰,表达量与对照组相比增加约50%。脑干在染毒12h处在最高峰,表达量比对照组增加约40%。GSH的测定结果显示,与对照组相比,大脑皮层GSH含量呈先降低后缓慢升高的趋势,显示出与Grp78变化相反的趋势。结论甲基汞急性暴露大鼠显示内质网应激具有时间效应和脑区特异性,这种内质网应激效应可能与氧化性应激有关。

英文摘要：

Objective To explore time-course effect and region-specificity of endoplasmic reticulum stress in rat brain acutely exposed by methylmercury（MeHg）.Methods Forty-two SD rats were randomly divided into seven groups,and the rats intraperitoneally injected at the dose of 4 mg /kg bw.MeHg were decapitated at the times of 0.5,1,3,6,12 and 24 h,then rats in control group intraperitoneally injected by the corresponding volume of normal saline were decapitated.The cerebellum,cerebral cortex,brain stem,hippocampus and striatum were dissected out and weighted on ice at once.The expressions of Grp78 protein which is a marker of endoplasmic reticulum stress,were determined by Western blotting analysis.The contents of reduced glutathione（GSH） of cerebral cortex were also determined.Results After exposure to MeHg,the tendencies of expression of Grp78 were consistent in various brain regions.It began to increase at the time of 0.5h and the peak levels reached at the times of 6h or 12h,then it began to decline.All expression levels returned nearly to the control levels at the time of 24h.The alternations of Grp78 protein in cerebral cortex and brain stem were statistically significant in comparison with those of control groups at the time of 0h among brain regions.Increases of Grp78 protein in cerebral cortex reached peak levels at the time of 6h after MeHg exposure,and the expressions of Grp78 protein corresponded to 150% of control levels.Increases of Grp78 protein in brain stem reached peak levels at the time of 12h after MeHg exposure,and the expressions of Grp78 protein corresponded to 140% of control levels.Further,the contents of GSH in cerebral cortex showed the tendencies of first decreases and then gradually showed increases.These changes were inversely correlated to the change of Grp78 protein in cerebral cortex（r =-0.77）.Conclusion Rats acutely exposed with MeHg could show endoplasmic reticulum stress in a time dependent and region-specific pattern,and this alteration could be associated with oxidative str