慢性酒精中毒大鼠海马神经元凋亡及caspase-8、AIF的表达升高

Hippocampal neuronal apoptosis and the increased expression of caspase-8 and AIF after chronic alcoholism in rats

目的观察慢性酒精中毒大鼠海马神经元凋亡及caspase-8、AIF蛋白表达情况,探讨慢性酒精中毒脑损伤可能的发病机制。方法清洁级8周龄雄性SD大鼠45只,随机分为对照组和酒精组,采用逐步增加浓度自由饮方法建立慢性酒精中毒大鼠动物模型。应用Morris水迷宫检测大鼠学习记忆功能,采用HE染色法观察海马神经元病理形态学改变,TUNEL法、免疫组化法检测凋亡神经元数量及caspase-8、AIF蛋白的表达。结果酒精组可见海马神经元数目缺失及细胞变性和损伤,其凋亡神经元数和caspase-8、AIF蛋白表达阳性细胞数均高于对照组(P<0.01)。结论慢性酒精中毒大鼠海马存在明显神经元凋亡,伴有caspase-8、AIF蛋白表达增加,通过caspase依赖性和非依赖性两种通路发生细胞凋亡可能是其病理基础之一。

Objective To investigate hippocampal neuronal apoptosis and the expression of caspase-8 and AIF protein in the model rats after chronic alcoholism.Methods Forty-five male SD rats,which were eight weeks old,were divided into two groups randomly： control group（n=20）and alcohol group（n=25）.The experiment adopted free drinking by increasing alcohol percentage gradually.Memory function of rats was detected by Morris water maze.Pathological changes were observed by HE staining,apoptosis cells and the expression of caspase-8 and AIF protein of each group were quantitatively examined by TUNEL and immunohistochemical method.Results In alcohol group,there are decrease and denaturalization of nerve cells in hippocampus.At the same time,the numbers of the neural apoptosis and the expression of caspase-8 and AIF protein in the alcohol group are higher than that of the control group（P0.01）.Conclusion There are obviously neural apoptosis as well as the expression of caspase-8 and AIF protein in the rats hippocampus after chronic alcoholism.One of mechanisms of cerebral trauma in chronic alcoholism maybe through both caspase-dependent and caspase-independent pathways.