麦门冬饮子对糖尿病模型小鼠认知功能障碍的影响及机制研究

Effect and Mechanism of Maimendong Yinzi on Cognitive Disorder in Diabetic Mice

目的:观察麦门冬饮子对糖尿病模型小鼠认知功能障碍的影响,并探讨其机制。方法:高脂高糖饲料联合腹腔注射STZ,诱导C57BL/6J小鼠制备糖尿病认知障碍模型,以不同剂量(5.06、10.13、20.25 g/kg)的麦门冬饮子水煎剂对小鼠进行灌胃,于给药后检测各试验小鼠空腹血糖(FPG),行为学测试水迷宫评估小鼠认知功能影响,ELISA法检测小鼠血清中糖基化血红蛋白(GHbA1c)、乙酰胆碱酯酶(AChE)、胆碱乙酰转移酶(ChAT)及海马组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平,HE染色观察海马组织病理改变,Western blot法检测小鼠脑组织中B淋巴细胞瘤-2基因(Bcl-2)、半胱氨酸蛋白酶-3(Cleaved-Caspase-3)、NADPH氧化酶亚基p67phox(p67phox)、尼克酰胺腺嘌呤二核苷酸磷酸氧化酶(gp91phox)蛋白表达。结果:与正常对照组比较,模型对照组小鼠的体重、平台穿越次数、血清ChAT水平、海马组织中SOD活性明显降低(P<0.05或P<0.01)、Bcl-2蛋白的表达明显下调(P<0.05或P<0.01);且小鼠空腹血糖、逃避潜伏期及探索距离、血清GHbA1c、AChE水平、海马组织中MDA含量明显升高(P<0.05或P<0.01)、p67phox、gp91phox、Cleaved-Caspase-3蛋白的表达明显上调(P<0.05或P<0.01)。与模型对照组相比,麦门冬饮子不同剂量组均能使小鼠的体重、平台穿越次数、血清ChAT水平、海马组织中SOD活性明显升高(P<0.05或P<0.01)、Bcl-2蛋白的表达显著上调(P<0.05或P<0.01);且空腹血糖、小鼠逃避潜伏期及探索距离、血清GHbA1c、AChE水平、海马组织中MDA含量明显下降(P<0.05或P<0.01)、p67phox、gp91phox、Cleaved-Caspase-3蛋白的表达显著下调(P<0.05或P<0.01)。结论:麦门冬饮子可以改善糖尿病认知功能障碍,其机制可能与抗氧化应激反应及调节细胞凋亡相关。

Objective:To investigate the effects of Maimendong Yinzi on treating the cognitive dysfunction in diabetic mice, and to explore its mechanism. Methods: Diabetic cognitive model was established by high-fat high glucose diet combined with STZ intraperitoneal injection in C57 BL/6 J mice. Mice were treated with different doses of Maimendong Yinzi(5.06 g/kg, 10.13 g/kg and 20.25 g/kg). Fasting blood glucose(FPG) was detected after administration. Water maze tests were used to assess the cognitive function, the serum levels of GHbA1 c, AChE and ChAT and the contents of SOD and MDA in hippocampus tissues were detected by ELISA,the hippocampal pathological changes were observed by staining, the protein expressions of Bcl-2,Cleaved-Caspase-3,p67 phox and gp91 phox were detected by Western blot method.Results:Compared with the control group, the body weight, the number of platform crossing, the serum ChAT level and SOD activity in hippocampus were significantly decreased(P<0.05 or P<0.01)in the model group, the Bcl-2 protein expression was significantly down regulated(P<0.05 or P<0.01), the fasting blood glucose, the escape latency and explore distance, the serum levels of GHbA1 c and AChE,the MDA content in hippocampus were significantly increased(P<0.05 or P<0.01), the protein expressions of p67 phox、gp91 phox and Cleaved-Caspase-3 were significantly up regulated(P<0.05 or P<0.01). Compared with the model group, the body weight, the number of platform crossing, the serum ChAT level and SOD activity were significantly increased(P<0.05 or P<0.01)in all doses of Maimendong Yinzi groups, Bcl-2 protein expression was significantly up regulated(P<0.05 or P<0.01),the fasting blood glucose, the escape latency and explore distance, the serum levels of GHbA1 c and AChE,the MDA content in hippocampus were significantly down regulated(P<0.05 or P<0.01), while the protein expressions of p67 phox, gp91 phox and Cleaved-Caspase-3 were significantly down regulated(P<0.05 or P<0.01).Conclusion:Maimendong Yinzi has the effect on cognitive dysfunction in diabetes mellitus, its mechanism may be related to the antioxidant stress response and the related regulation of cell apoptosis.