有氧运动调控自噬改善动脉粥样硬化小鼠心肌纤维化机制研究

关键词：有氧运动  动脉粥样硬化  心肌组织  自噬  纤维化

Keywords:aerobic exercise  atherosclerosis  myocardial tissue  autophagy  fibrosis

摘要：

      摘要 目的：探讨有氧运动调控自噬改善动脉粥样硬化小鼠心肌纤维化的机制。 方法：选8周龄雄性ApoE-/-基因敲除小鼠，适应性饲喂1周后，随机分为模型组、有氧运动组和空白对照组，每组9只；饲以“西方类型”膳食饲料喂养12周，建立动脉粥样硬化模型，有氧运动组同时进行有氧训练。12周后采用油红O染色观察两组小鼠动脉粥样硬化病理情况，Masson染色检测各组小鼠的心肌纤维化情况；免疫荧光检测各组小鼠心肌组织ATG5、LC3BⅡ/Ⅰ、Beclin-1、p62的表达和定位；Western Blot检测各组小鼠心肌组织中ATG5、LC3BⅡ/Ⅰ、Beclin-1、p62的蛋白水平。 结果：油红O染色显示，模型组发现明显的粥样斑块形成，而有氧运动组动脉粥样硬化斑块面积明显少于模型组，动脉粥样硬化程度明显改善。Masson染色显示有氧运动组心肌纤维化较模型组明显改善，且两组心肌纤维化程度均重于空白对照组；免疫荧光和Western Blot检测显示，有氧运动组小鼠心肌组织ATG5、LC3BⅡ/Ⅰ、Beclin-1表达量显著升高，p62蛋白水平明显降低（P<0.05）。 结论：有氧运动明显改善动脉粥样硬化小鼠心肌纤维化程度，其机制可能与有氧运动激活小鼠心肌组织自噬相关因子有关。

Abstract:

      Abstract Objective： To explore the mechanism of aerobic exercise regulating autophagy to improve myocardial fibrosis in mice with atherosclerosis. Method： Eight weeks old male ApoE-/- knockout mice were randomly divided into model group， aerobic exercise group and blank control group after one-week adaption， with nine mice in each group. The atherosclerosis model was established by fed a “Western type” diet for 12 weeks and the aerobic exercise group was received aerobic training at the same time. After 12 weeks， Oil Red O staining was used to observe the pathological status of atherosclerosis in the two groups， and Masson dyeing was used to detect myocardial fibrosis in each group. The expressions and localization of ATG5， LC3BⅡ/Ⅰ， Beclin-1 and p62 in myocardial tissue of mice in each group were detected by immunofluorescence. The protein levels of ATG5， LC3BⅡ/Ⅰ， Beclin-1 and p62 in myocardial tissue of each group were detected by Western Blot. Result： Oil red O staining showed that obvious atherosclerotic plaque formation was found in the model group， while the area of atherosclerotic plaque in the aerobic exercise group was significantly less than that in the model group， indicating the degree of atherosclerosis was significantly improved. Masson dyeing showed that myocardial fibrosis in the aerobic exercise group was significantly improved compared with the model group， and the degree of myocardial fibrosis in both groups was greater than that in the blank control group. Immunofluorescence and Western Blot analysis showed that the expression levels of ATG5， LC3B II/I， and Beclin-1 in the myocardial tissue of aerobic exercise group mice were significantly increased， while the level of p62 protein was significantly reduced （P<0.05）. Conclusion： Aerobic exercise can significantly improve myocardial fibrosis in mice with atherosclerosis， and the mechanism may be related to aerobic exercise activated autophagy-related factors in myocardial tissue of mice.