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

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,Bcl-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,Bcl-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),Bcl-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Bcl-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Bcl-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.

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

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 (P<0.01), and swimming time in the platform of previous quadrant was significantly shorter in model group (P<0.01). Furthermore, the expression of Bcl-2 protein was decreased, while Caspase-3 and Bax in the hippocampus were increased compared with the control group (P<0.01). 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 (P<0.01 or P<0.05). 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.