血糖波动对糖尿病大鼠海马神经元凋亡相关蛋白表达的影响

Effects of fluctuant high blood glucose on the expression of apoptosis-related genes in neurons of hippocampus of diabetic rats

目的观察糖尿病大鼠在血糖波动状态下海马神经元的病理形态学改变及BCL-2、BAX的异常表达,探讨血糖波动对糖尿病大鼠海马神经元的影响。方法用链脲佐菌素(STZ)诱导,间断短效胰岛素应用制备糖尿病血糖波动模型。12周后,用免疫组化法检测海马神经元凋亡蛋白BCL-2、BAX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N组显著下降,BAX显著升高(P<0.01),出现锥体细胞退变的典型病理改变。RDM组BCL-2的表达较DM组进一步下降,BAX进一步升高(P<0.05),病理改变较DM组进一步加重。结论糖尿病大鼠血糖波动可明显加速海马CA1区神经元凋亡,BCL-2、BAX的异常表达可能是糖尿病大鼠海马神经元损伤机制之一。

Objective To investigate the effect of fluctuant high blood glucose on the pathology profile and BCL-2, BAX expression in neurons of the hippocampus from diabetic rats. Methods The diabetic rat models were developed by injection with 1% streptozotocin （STZ）, followed by insulin administration. Regular insulin was used to set up fluctuant high glucose group model. After 12 experimental weeks, the expression of Fas protein in hippocampus was checked by immunohistochemistry, pathological changes and ultrastructure were observed by using light micros-copy and electron microscopy in three groups. Results Compared with those in N group, the expression of BCL-2 in pyramidal cells of diabetic rat＇s hippocampus was lower,while that of BAX was higher （P 〈0.01）. The pathologic change of retrogression was significantly serious. The pathologic change in RDM group was more serious in fluctuant high blood glucose rats group （ P 〈 0.05）. Conclusion Fluctuant high blood glucose induces more apoptosis in hippocampal neurons cells. The expression of BCL-2 and BAX may be one of the mechanisms that mediates hippocampus neuron injury in diabetic rats.