银杏叶提取物对糖尿病性脑病大鼠海马细胞凋亡的影响

Effect of Ginkgo biloba extracts on hippocampal apoptosis in diabetic encephalopathy rat

目的研究糖尿病性脑病与海马区细胞凋亡的关系以及银杏叶提取物(EGb)治疗的效果和机制。方法大鼠分为对照(NC)组、糖尿病性脑病(DM+B)组和EGb治疗(EGb)组,分1个月和3个月两个时间点。水迷宫实验观察行为学改变,免疫组化、RT-PCR检测Bc1-2和Bax蛋白及mRNA的表达,ELISA检测脑组织细胞凋亡的水平。结果 (1)DM+B_1组已出现学习、记忆功能障碍,DM+B_3组更加加重,EGb组则明显减轻。(2)DM+B_1、DM+B_3组Bc1-2表达较NC组增加,EGb_1、EGb_3组表达更强。(3)DM+B_1、DM+B_3组Bax表达较对照组明显增加,EGb_1、EGb_3组则明显减弱。(4)DM+B_1组脑组织细胞凋亡水平升高,DM+B_3组更加明显,治疗组则显著减轻。结论海马区细胞凋亡是糖尿病性脑病发病的重要因素,银杏叶提取物可能通过抑制细胞凋亡而对糖尿病性脑病有保护作用。

Objective To study the relation between diabetic rat eneephalopathy and hippocampal apoptosis, and the therapeutic effect and mechanism of Ginkgo biloba extract. Methods Sixty rats were assigned into control group （NC）, diabetic encephalopathy group （DM ＋ B） and EGb-treatment group （EGb） randomly, and every group was further divided into two time points of 1 month （NC1, DM＋ B1 , EGbl ） and 3 month（NCa ,DM＋B3 ,EGb3）. The behavioral abnormalities were investigated by water maze test and the apoptosis levels of brain tissue by ELISA. Immunohistochemistry and RT-PCR were performed to determine the protein and mRNA expressions of Bcl-2 and Bax. Results （1） Mild dysfunction of learning and memory was detected in DM＋B1 group, and the dysfunction became worse in DM＋B3 group. The matters were greatly improved in EGb-treatment groups. （2） The expressions of Bcl- 2 protein and mRNA were increased in DM-B1, and DMd-Ba groups, and were stronger in EGb, and EGb3 groups. （3） The expressions of Bax protein and mRNA were obviously increased in DM＋B1 and DM＋B3 groups, and were dramatically reduced in EGb, and EGb3 groups. （3.） Compared with control group, the apoptosis level of brain tissue was increased in DM＋B1 group, and obviously greater in DM＋B3 group. In the EGb-treatment groups the levels were dramatically reduced. Conclusions Diabetic encephalopathy may be closely related to hippocampal apoptosis. EGb has an protective effect and the mechanism may be attributed to its effects inhibiting apoptosis.