KLF15/mTOR相关蛋白在有氧间歇性运动改善2型糖尿病大鼠骨骼肌病变中的作用*

doi:10.12047/j.cjap.6350.2022.123

摘要/Abstract

摘要： 目的: 研究有氧间歇运动调节KLF15/mTOR相关蛋白表达改善2型糖尿病大鼠骨骼肌病变的作用。方法: 采用高脂饲料喂养4周配合腹腔注射链脲佐菌素的方法制备2型糖尿病大鼠实验模型。成模后,大鼠随机分为2组:糖尿病模型组(DM)、糖尿病+运动组(DE),另设对照组(C)。每组10只。DE组给予8周有氧间歇跑台运动干预,C组不施加任何干预。实验末,采用Western blot法检测腓肠肌KLF15、mTOR 、p-mTOR、cleaved caspase-3表达,HE染色、TUNEL荧光染色法等分别观察腓肠肌形态结构,骨骼肌细胞凋亡和肌质量的变化,同时测试血糖、血胰岛素指标。结果: ①与C组比较,DM组腓肠肌湿重、体重和腓肠肌湿重/体重比值均显著降低(P＜0.05或P＜0.01);与DM组比较,DE组腓肠肌湿重、腓肠肌湿重/体重比值显著增加(均P＜0.05)。②与C组比较,DM组空腹血糖显著升高(P＜0.01),胰岛素水平显著降低(P＜0.01);与DM组比较,DE组空腹血糖水平显著降低(P＜ 0.05),胰岛素水平显著增加(P＜0.05)。③与C组比较,病理观察DM组骨骼肌细胞形态异常,肌核增多,横纹模糊消失,肌节出现节断性损伤、部分肌纤维有溶解等现象;与DM组比较,DE组的细胞形态异常、肌节的节断性损伤和肌纤维的溶解等现象均有一定程度改善,肌膜较完整、肌核排列渐趋整齐。④与C组比较,DM组骨骼肌KLF15、细胞凋亡率和cleaved caspase-3蛋白表达显著升高(P＜0.01),p-mTOR/mTOR水平显著降低(P＜0.01);与DM组比较,DE组的KLF15、细胞凋亡率和cleaved caspase-3表达显著降低(P＜0.05或P＜0.01),该组的p-mTOR/mTOR水平显著增加(P＜0.05)。结论: 有氧间歇运动有利于改善2型糖尿病大鼠骨骼肌病变,其原因可能是通过有效调节KLF15/mTOR相关蛋白表达,一定程度减少细胞凋亡损伤实现。

关键词: 2型糖尿病, 有氧间歇运动, 骨骼肌病变, KLF15/mTOR相关蛋白, 大鼠

Abstract: Objective: To investigate the effects of aerobic intermittent exercise on the expressions of KLF15/mTOR related proteins to improve skeletal muscle lesions in type 2 diabetes rats. Methods: The experimental model of type 2 diabetes rats was established by feeding high-fat diet for 4 weeks and intraperitoneal injection of streptozotocin (STZ). After modeling, rats were randomly divided into two groups: diabetes model group (DM), diabetes+exercise group (DE), and normal rats were set as control group (C), 10 rats in each group. Group DE was given 8-week aerobic intermittent treadmill exercise intervention, while group C was not given any intervention. At the end of the experiment, the expressions of KLF15, mTOR, p-mTOR, and cleared caspase-3 in gastrocnemius muscle were detected by Western blot. The histopathologic changes of gastrocnemius were observed under microscope; skeletal muscle cells apoptosis rates and muscle mass were examined respectively using HE staining and TUNEL fluorescence staining. At the same time, changes of blood glucose and serum insulin, and weight were examined in the end of the experiment. Results: ①Compared with group C, the wet weight of gastrocnemius muscle and body weight, ratio of wet gastrocnemius muscle and body weight in group DM were decreased(P＜0.05 or P＜0.01); compared with group DM, the wet weight of gastrocnemius muscle, ratio of wet gastrocnemius muscle and body weight in the group DE were increased significantly (P＜0.05). ②Compared with group C, the fasting blood glucose level of group DM was increased significantly (P＜0.01), while serum insulin level of the group DM was decreased significantly(P＜0.01);compared with group DM, the above indexes were opposite in the group DE with intervention(P＜0.05). ③Compared with group C, the morphology of skeletal muscle cells in group DM was abnormal, the number of muscle nuclei was increased, the transverse lines were blurred and disappeared, the sarcomere was broken, and some muscle fibers were dissolved. Compared with group DM, the abnormal cell morphology, segmental injury of sarcomere and dissolution of muscle fibers in group DE were improved. The sarcolemma was more complete and the arrangement of muscle nuclei was more orderly. ④Compared with group C, the expressions of KLF15 and cleaved caspase-3, cells apoptosis rates in group DM were increased significantly(P＜0.01), while p-mTOR/mTOR level was decreased(P＜0.01) ; compared with group DM, the above indexes were opposite in the group with intervention(P＜0.05 or P＜0.01). Conclusion: Aerobic intermittent exercise is beneficial to improve the skeletal muscle pathological changes in type 2 diabetes rats, which may be due to the effective regulation of KLF15/mTOR related protein expression and the reduction of apoptosis damage.

Key words: diabetes mellitus, aerobic interval training, skeletal muscle lesions, KLF15/mTOR related proteins, rats

中图分类号:

G804.5
R49

廖忠鑫, 黄蕾, 朱洪竹, 朱梅菊. KLF15/mTOR相关蛋白在有氧间歇性运动改善2型糖尿病大鼠骨骼肌病变中的作用^*[J]. 中国应用生理学杂志, 2022, 38(6): 676-681.

LIAO Zhong-xin, HUANG Lei, ZHU Hong-zhu, ZHU Mei-ju. KLF15/mTOR related proteins involved in effect of aerobic interval training on improving skeletal muscle lesions in rats with type 2 diabetes[J]. CJAP, 2022, 38(6): 676-681.

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KLF15/mTOR相关蛋白在有氧间歇性运动改善2型糖尿病大鼠骨骼肌病变中的作用^*

KLF15/mTOR related proteins involved in effect of aerobic interval training on improving skeletal muscle lesions in rats with type 2 diabetes

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