针刺对阿尔茨海默病模型小鼠行为学及线粒体分裂蛋白1、融合蛋白1表达和超微结构的影响

Effects of Acupuncture on Behaviors, Expressions of Fis1 and OPA1, and Mitochondrial Ultrastructure of Mice Model of Alzheimer Disease

目的观察针刺对阿尔茨海默病(AD)模型小鼠行为学,大脑海马神经元线粒体分裂蛋白1(Fis1)、线粒体融合蛋白1(OPA1)表达及线粒体超微结构的影响,探讨针刺治疗AD的作用机制。方法 40只雄性SAMP8小鼠随机分为针刺组和模型组,每组20只。另取20只同月龄雄性正常老化模型小鼠(SAMR1小鼠)作为正常组,针刺组选取"肾俞""百会""血海""膈俞"进行干预。8周后,Morris水迷宫实验检测小鼠行为学,之后提取海马组织,Western blot检测小鼠海马线粒体相关蛋白Fis1和OPA1的表达,电镜观察小鼠海马神经元线粒体超微结构。结果与模型组比较,针刺组逃避潜伏期明显缩短(P<0.05),其停留在原平台象限时间延长和穿越原平台次数明显增加(P<0.05);针刺组Fis1表达明显减弱,OPA1表达明显增强(P<0.05,P<0.01);针刺组线粒体超微结构明显改善,线粒体体密度及面密度明显增加(P<0.05)。结论针刺可能通过提高模型小鼠学习记忆能力、下调Fis1表达、上调OPA1表达和改善线粒体超微结构,达到治疗AD的作用。

Objective To observe the effects of acupuncture on the behaviors and the expressions of Fis1 and OPA1, as well as mitochondrial ultrastructure in the hippocampus of mice with Alzheimer disease （AD）; To explore the mechanism of action of acupuncture for AD. Methods Forty male SAMP8 mice were randomly divided into acupuncture group and model group, with 20 mice in each group. Another 20 male natural aging mice with the same age （SAMR1 mice） were set as the normal group. Acupuncture group chose Shenshu, Baihui, Xuehai and Geshu for intervention. 8 weeks later, Morris water maze was used to test the mice behaviors, and then hippocampus organization was taken. Western blot was used to detect the expressions of Fis1 and OPA1 and mitochondrial ultrastructure in hippocampal neurons of mice was observed by transmission electron microscopy. Results Compared with the model group, the escape latency of acupuncture group was significantly shortened （P〈0.05）, and the stay time in the former platform quadrant and former platform crossing times were significantly increased （P〈0.05）. The expression of Fis1 in the hippocampus of acupuncture group decreased significantly （P〈0.05）, while the expression of OPA1 increased significantly （P〈0.05）. The mitochondrial ultrastructure in hippocampus in the acupuncture group was effectively improved, and the mitochondrial surface density and body density were both increased in the acupuncture group compared with the model group （P〈0.05）. Conclusion Acupuncture may play a potential therapeutic role in AD by decreasing the expression of Fis1, increasing the expression of OPA1, recovering the injury of mitochondrial ultrastructure.