高强度间歇运动训练上调APP/PS1转基因阿尔兹海默病小鼠海马线粒体自噬的研究

关键词：APP/PS1转基因鼠  阿尔兹海默病  高强度间歇运动训练  线粒体自噬  脑海马

Keywords:APP/PS1 transgenic mice  Alzheimer's disease  high-intensity interval training  mitophagy  hippocampus

摘要：

      摘要 目的：观察高强度间歇运动训练干预是否能改善APP/PS1转基因AD小鼠病理表现，并探讨线粒体自噬在其间的生物学效应。 方法：8月龄雄性APP/PS1转基因小鼠分为转基因模型安静组（SED-Tg）和转基因模型+高强度间歇运动训练组（HIIT-Tg），C57BL/6 野生型小鼠纳入野生型安静组（SED-Wt）。HIIT-Tg组动物进行12周高强度间歇运动训练。避暗被动回避实验检测学习记忆能力，JC-1荧光探针检测海马线粒体膜电位，二氯荧光素探针检测海马线粒体ROS，Western Blot法检测脑海马Aβ-42、BDNF、AMPK、PINK1、Parkin、Bnip3蛋白表达。 结果：①SED-Tg组与SED-Wt组比较，逃避潜伏期、线粒体膜电位、BDNF、AMPK、PINK1、Parkin和Bnip3蛋白表达显著降低（P<0.05—0.01），线粒体ROS产生速率和Aβ-42蛋白表达显著升高（P<0.01）。②HIIT-Tg组与SED-Tg组比较，逃避潜伏期、线粒体膜电位、BDNF、AMPK、PINK1和Parkin蛋白表达显著升高（P<0.01），线粒体ROS产生速率和Aβ-42蛋白表达显著降低（P<0.01）。 结论：高强度间歇运动训练可通过上调AMPK- PINK1/Parkin介导的线粒体自噬，改善线粒体功能，减少APP/PS1转基因AD小鼠脑海马Aβ积聚，提高记忆和学习能力。

Abstract:

      Abstract Objective: To observe the effect of high-intensity interval training on hippocampus in APP/PS1 transgenic mice， as well as the role of mitophagy. Method: Male 8-month APP/PS1 transgenic mice were divided into two groups: sedentary APP/PS1 transgenic mice group (SED-Tg)， and high-intensity interval training APP/PS1 transgenic mice group (HIIT-Tg). C57BL/6 wile-type mice were placed in sedentary wild type mice group (SED-Wt). HIIT-Tg mice were subjected to a high-intensity interval training for 12 weeks. Learning ability and memory were evaluated by passive avoidance test. Mitochondrial membrane potential was measured by JC-1 probe. Mitochondrial ROS production was monitored using the dichlorofluorescin diacetate. The protein expressions of Aβ-42， BDNF， AMPK， PINK1， Parkin and Bnip3 were detected by western blotting. Result: ①Comparing with SED-Wt group， the retention latency time， membrane potential， protein expressions of BDNF， AMPK， PINK1， Parkin and Bnip3 showed dramatic decrease in SED-Tg group(P<0.05—0.01)， while ROS production and Aβ-42 level increased significantly (P<0.01). ②Comparing with SED-Tg group，the retention latency time， membrane potential， protein expressions of BDNF， AMPK， PINK1 and Parkin showed dramatic increase in HIIT-Tg group (P<0.01)， while ROS production and Aβ-42 level decreased significantly (P<0.01). Conclusion: High-intensity interval training could enhance AMPK -PINK1/Parkin -mediated mitophagy， which in turn ameliorate mitochondrial dysfunction， Aβ deposition and cognitive impairment in hippocampus of APP/PS1 transgenic mice.