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

Zhong-Xin Liao, Lei Huang, Hong-Zhu Zhu, Mei-Ju Zhu
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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.

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[KLF15/mTOR相关蛋白参与有氧间歇训练对改善2型糖尿病大鼠骨骼肌病变的影响]。
目的:探讨有氧间歇运动对KLF15/mTOR相关蛋白表达的改善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,腹腔注射链脲佐菌素(STZ)建立2型糖尿病大鼠实验模型。造模后,将大鼠随机分为糖尿病模型组(DM)、糖尿病+运动组(DE)和正常大鼠为对照组(C),每组10只。DE组给予8周有氧间歇跑步机运动干预,C组不给予干预。实验结束时,采用Western blot法检测大鼠腓肠肌中KLF15、mTOR、p-mTOR、cleared caspase-3的表达。显微镜下观察腓肠肌组织病理变化;采用HE染色和TUNEL荧光染色分别检测骨骼肌细胞凋亡率和肌肉质量。同时在实验结束时检测血糖、血清胰岛素和体重的变化。结果:①与C组相比,DM组大鼠腓肠肌湿重与体重、腓肠肌湿重与体重之比均显著或极显著降低(P<0.05或P<0.01);与DM组相比,DE组腓肠肌湿重、湿腓肠肌与体重的比值显著升高(P<0.05)。②与C组相比,DM组空腹血糖水平显著升高(P<0.01),血清胰岛素水平显著降低(P<0.01);与DM组相比,DE干预组上述指标均相反(P<0.05)。③与C组比较,DM组骨骼肌细胞形态异常,肌核增多,横线模糊消失,肌节断裂,部分肌纤维溶解。与DM组比较,DE组细胞形态异常、肌节段性损伤和肌纤维溶解程度均有所改善。肌膜更完整,肌核排列更有序。④与C组比较,DM组KLF15、cleaved caspase-3的表达及细胞凋亡率显著升高(P<0.01), P -mTOR/mTOR水平显著降低(P<0.01);干预组与DM组相比,上述指标均相反(P<0.05或P<0.01)。结论:有氧间歇运动有利于改善2型糖尿病大鼠骨骼肌病理改变,其机制可能与有效调节KLF15/mTOR相关蛋白表达,减轻细胞凋亡损伤有关。
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