胰岛素对脑缺血后鼠海马CA1区神经元凋亡及记忆影响

The effect of insulin on the apoptosis of neuron in hippocampal CA1 region and the change of memory of rat post global brain ischemia

目的 观察胰岛素对全脑缺血后海马CA1区神经元凋亡及大鼠学习记忆力改变的影响 ,探讨胰岛素对全脑缺血后海马CA1区神经元产生中枢直接保护作用的机理。方法 利用 4 VO法制作大鼠全脑缺血模型。造成脑缺血 15min后行再灌注 ,于再灌注后即刻经脑室注入 1U胰岛素 ,利用免疫组化及原位标记法分别于全脑缺血后 1、3d观察海马CA1区Bcl 2、Bcl xl蛋白表达及神经元凋亡的情况 ;缺血后 8周 ,利用“Y”型迷宫测试大鼠的学习记忆功能。结果 全脑缺血后 3d ,缺血组大鼠海马CA1区Bcl 2、Bcl xl蛋白的表达呈阴性 ,海马CA1区原位标记阳性细胞计数为 14 3.5± 11.6。治疗组大鼠海马CA1区Bcl 2、Bcl xl蛋白呈阳性表达 ,海马CA1区原位标记阳性细胞计数为 75 .6±6 .7。全脑缺血后 8周 ,治疗组大鼠学习记忆力明显好于缺血组。结论 全脑缺血后脑室内注入胰岛素可促进海马CA1区Bcl 2、Bcl xl蛋白表达 ,减少神经元的凋亡 ,进而减轻脑缺血后大鼠的学习记忆力损害 。

Objective To investigate the mechanism of neuroprotective effect of insulin on hippocamal CA1 region, the expression of Bcl 2, Bcl xl protein and the apoptosis of neuron in hippocampal CA1 region, as well as the change of memory of rat following global brain ischemia were observed. Methods Four vessels' occlusion was used to establish the rat global brain ischemic model. After brain ischemia for 15 minutes, one unit of insulin was injected into the brain ventricle immediately post reperfusion. In 1 and 3 days post brain ischemia, the expression of Bcl 2, Bcl xl protein and the apoptosis of neuron in hippocampal CA1 region were detected by immunocytochemistry and in situ end labeling (ISEL) method respectively. The ability of memory of rat was tested by 'Y' maze 8 weeks post brain ischemia. Results In three days post brain ischemia, the expression of Bcl 2, Bcl xl protein was negative in ischemic group and the count of positive cells labeled by ISEL was 143.5±11.6, while the expression of Bcl 2 , Bcl xl protein was positive in treated group and the count of positive cells labeled by ISEL was 75.6±6.7. In 8 weeks post brain ischemia, the ability of memory of rat in ischemic group was poorer than that in treated group.Conclusion Intraventricular administration of insulin can improve the expression of Bcl 2, Bcl xl protein, reduce the apoptosis of neuron in rat hippocampal CA1 region and attenuate the memory deficits of rat post brain ischemia. This may be one of the main mechanisms of insulin to achieve the neuroprotective effect on hippocamal CA1 region post global brain ischemia.