脑康Ⅱ号对糖尿病大鼠认知功能及海马区凋亡相关蛋白表达的影响

Effects of Naokang Erhao decoction on cognitive ability and hippocampal apoptosis-related proteins in diabetic rats

目的:探讨脑康Ⅱ号对2型糖尿病大鼠认知功能,海马CA1区Caspase-3,Bc l-2和Bax蛋白表达的影响及其治疗糖尿病认知障碍的可能作用机制。方法:高糖高脂饮食结合腹腔注射链脲佐菌素诱发糖尿病大鼠模型,并用3种不同剂量的脑康Ⅱ号治疗4周。采用Morris水迷宫法进行行为学检测,用免疫组化法检测海马CA1区凋亡相关蛋白Caspase-3,Bc l-2和Bax的表达水平。结果:与正常对照组相比,糖尿病模型组Morris水迷宫平均逃避潜伏期和游泳距离均明显延长(P<0.01),空间探索实验中在原平台所在象限游泳时间明显缩短(P<0.01),表明学习记忆能力显著下降;模型组海马CA1区凋亡相关蛋白Caspase-3和Bax表达增多(P<0.01),Bc l-2表达减少(P<0.01)。经过脑康Ⅱ号各剂量组(分别含生药0.5,1.0,2.0 g.mL-1)灌胃治疗4周,糖尿病大鼠学习记忆能力显著改善(P<0.01或P<0.05),海马CA1区Bc l-2表达显著上调(P<0.01或P<0.05),Caspase-3和Bax表达明显减少(P<0.01或P<0.05)。结论:脑康Ⅱ号对2型糖尿病大鼠脑神经细胞的保护作用可能是通过上调Bc l-2蛋白、下调Caspase-3和Bax蛋白的表达,抑制细胞凋亡而实现,进而改善2型糖尿病大鼠的学习记忆能力。

Objective：To investigate the effects of Naokang Erhao decoction on the cognitive ability and the expression of Caspase-3,Bax and Bcl-2 proteins in hippocampus of type 2 diabetic rats.Method：The diabetes mellitus（DM） rat model was produced by intraperitoneal injection of streptozotocin and fed with high fat and sucrose diet.The Naokang Erhao-treated rats were intragastrically given different doses of Naokang Erhao,whereas the control and DM model groups were given double distilled water for 4 consecutive weeks.Learning and memory abilities of rats were tested with the Morris water maze.The expression of Caspase-3,Bax and Bcl-2 proteins in hippocampal CA1 region was measured by immunohistochemistry.Result：Both escape latency and swimming distance of type 2 DM rats were significantly prolonged in comparison of those in normal control（P0.01）,and swimming time in the platform of previous quadrant was significantly shorter in model group（P0.01）.Furthermore,the expression of Bcl-2 protein was decreased,while Caspase-3 and Bax in the hippocampus were increased compared with the control group（P0.01）.Four weeks of treatment with Naokang Erhao decoction remarkably improved the learning and memory abilities of DM rats,increased the expression of Bcl-2 and decreased the expression of Caspase-3 and Bax in hippocampal CA1 region of model rats（P0.01 or P0.05）.Conclusion：Naokang Erhao decoction may inhibit apoptosis by increasing the expression of Bcl-2 and reducing the expression of Caspase-3 and Bax in the hippocampus,and this may be one of the mechanisms by which Naokang Erhao decoction improves cognitive ability in DM rats.