胰岛素对糖尿病大鼠海马神经元凋亡相关蛋白表达的影响

目的观察糖尿病大鼠海马神经元的病理形态学改变和BCL-2、BAX、caspase-3的异常表达及胰岛素干预后的影响。方法用链脲佐菌素（STZ）诱导制备糖尿病动物模型，每日长效胰岛素应用制备糖尿病胰岛素治疗动物模型。随机分为3组：高血糖组（DM组）、胰岛素治疗组（PDM组）、对照组（NC组）。12周后，用免疫组化法检测海马神经元凋亡蛋白BCL-2、BAX、caspase-3的表达，分别在光镜、透射电镜下观察各组海马神经元病理形态学改变及超微结构的变化。结果DM组BCL-2的表达较NC组显著下降，BAX、caspase-3显著升高（P〈0．05），出现锥体细胞退变的典型病理改变。PDM组BCL-2的表达较DM组有所增高，BAX、caspase-3有所下降（P〈0．05），病理改变较DM组有所改善。结论高血糖可引起海马神经元凋亡，胰岛素通过逆转糖尿病大鼠海马神经元caspase-3、BAX的表达，增加BCL-2的表达，对糖尿病脑病起保护作用。

Effects of insulin therapy on the expression of apoptosis-related proteins in the hippocampal neurons in diabetic rats

Objective To observe the pathomorphological changes of the hippocampal neurons of diabetic rats and the abnormal expressions of BCL - 2, BAX and caspase - 3 and to investigate the effect of insulin intervention. Methods The diabetic rat models were established by injection of 1% streptozotoein （ STZ）, followed by administration of protamine Zinc insulin to establish insulin therapy model. The rats were randomized into three groups： high blood glucose group （DM）, insulin treatment group （PDM group） and the control group （NC group）. At the end of 12 weeks, the expressions of apoptins BCL - 2, BAX and caspase - 3 in the hippocampus was studied by immunohistochemistry. The changes of pathology and ultrastructure in the three groups were observed by light microscopy and transmission electron microscopy, respectively. Results Compared with NC group, the expression of BCL - 2 in pyramidal cells in rat hippo- campus in DM group markedly decreased, while expressions of BAX and caspase - 3 significantly increased （ P 〈 0.05 ） , with typical pathological changes as retrogression of pyramidal cells. Compared with DM group, the BCL - 2 expression in PDM group was upregulated and the expressions of BAX and caspase - 3 were downregulated （ P 〈 0.05 ） , and the pathological changes were relieved by protamine zinc insulin treatment. Conclusion High blood glucose induces apoptosis in hippoeampal neurons, while insulin has protective effects on hippocampus of diabetic rats by reversing the expressions of easpase- 3 and BAX and up -regulating BCL- 2.