Myostatin信号通路在4周离心耐力运动改善2型糖尿病大鼠骨骼肌萎缩中的作用

doi:10.12047/j.cjap.5632.2018.053

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (3): 223-228.doi: 10.12047/j.cjap.5632.2018.053

Myostatin信号通路在4周离心耐力运动改善2型糖尿病大鼠骨骼肌萎缩中的作用

王继, 周越, 张荷, 李文博, 黄怡

北京体育大学运动人体科学学院, 北京 100084

收稿日期:2017-09-18 修回日期:2017-12-20 出版日期:2018-05-28 发布日期:2018-09-08
通讯作者: 周越,E-mail:chowyue@163.com E-mail:chowyue@163.com
基金资助:
中央高校基本科研业务费专项资金资助（2016ZD003，2017XS019）

The role of myostatin signaling pathway in improvement of skeletal muscle atrophy in type 2 diabetic rats after 4 weeks of eccentric endurance exercise

WANG Ji, ZHOU Yue, ZHANG He, LI Wen-bo, HUANG Yi

Sport Science College, Beijing Sport University, Beijing 100084, China

Received:2017-09-18 Revised:2017-12-20 Online:2018-05-28 Published:2018-09-08
Supported by:
中央高校基本科研业务费专项资金资助（2016ZD003，2017XS019）

摘要/Abstract

摘要： 目的：观察4周离心耐力运动对2型糖尿病大鼠代谢障碍及肌萎缩的影响，探讨myostatin/Smad3/atrogin-1信号通路在肌萎缩中的作用。方法：9周高脂饲养联合STZ注射建立2型糖尿病大鼠模型。将普通饲料组大鼠随机分为对照组（C，n=6）和运动组（E，n=9；将2型糖尿病模型组大鼠随机分为糖尿病对照组（D，n=8）和糖尿病运动组（DE，n=12）。运动方案：坡度-5°，跑速16 m/min，每次60 min、每日一次，每周训练5 d，连续4周。最后一次运动后禁食12 h，测定空腹血糖（FBG）、空腹胰岛素（FINS），计算稳态模式胰岛素抵抗指数（HOMA-IR）和胰岛素敏感指数（ISI），进行葡萄糖耐量试验。取比目鱼肌观察肌萎缩现象并检测myostatin、Smad3、p-Smad3和atrogin-1表达情况。结果：①与对照组相比，糖尿病组大鼠体重、比目鱼肌质量/胫骨长和肌纤维平均横截面积、FINS和ISI显著降低（P<0.01），FBG、HOMA-IR和血糖曲线下面积（AUC_BG）以及myostatin、Smad3、p-Smad3、atrogin-1表达均显著升高（P<0.01）。②4周离心运动后，与糖尿病组相比，糖尿病运动组大鼠肌纤维平均横截面积显著升高（P<0.01），AUC_BG、HOMA-IR及myostatin、p-Smad3、atrogin-1表达显著降低（P<0.05，P<0.01）。结论：myostatin/Smad3/atrogin-1信号通路上调是导致2型糖尿病肌萎缩的重要原因，4周离心耐力运动可能通过下调myostatin、p-Smad3和atrogin-1表达抑制肌萎缩，进而改善2型糖尿病代谢障碍，提高胰岛素敏感性。

关键词: 离心耐力运动, 2型糖尿病, 大鼠, 肌萎缩, 肌肉生长抑素

Abstract: Objective: To observe the effect of 4 weeks eccentric endurance exercise on metabolic disturbance and muscle atrophy in type 2 diabetic rats, and to investigate the role of myostatin/Smad3/atrogin-1 signaling pathway in muscle atrophy.Methods: Type 2 diabetic rats were established by high fat diet combined with streptozotocin(STZ) injection for 9 weeks. The normal chow diet rats were randomly divided into control group (C, n=6) and exercise group (E, n=9), the type 2 diabetic mellitus rats were randomly divided into diabetic control group (D, n=8) and diabetic exercise group (DE, n=12). Exercise program:slope of -5°, speed of 16 m/min, 60 min each time, 1 time a day, 5 d per week for 4 weeks. Fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (homeostasis model assessment insulin resistance index, HOMA-IR), insulin sensitivity index (insulin sensitivity index, ISI) and glucose tolerance test were measured on fasting 12 hours after exercise. Soleus muscle was drawed after exercise and the degree of muscle atrophy was detected. The expressions of myostatin, phospho-Smad3 (p-Smad3), drosophila mothers against decapentaplegic protein 3 (Smad3) and atrogin-1 were detected.Results: ①Compared with control group, body weight, soleus mass/tibia length, muscle fiber cross-sectional area, FINS and ISI of diabetic group rat were decreased significantly (P<0.01), FBG, HOMA-IR, area under the curve of blood glucose (AUC_BG), the expression of all myostatin, Smad3, p-Smad3 and atrogin-1 was increased significantly (P<0.01). ②After 4 weeks of eccentric exercise, compared with diabetic group, muscle fiber cross-sectional area of diabetic exercise group rat was increased significantly(P<0.01). AUC_BG, HOMA-IR, the expression of myostatin, p-Smad3 and atrogin-1 were decreased significantly (P<0.05, P<0.01).Conclusion: The up-regulation of myostatin/Smad3/atrogin-1 signaling pathway is an important cause of muscle atrophy in type 2 diabetes. The down-regulation of myostatin, p-Smad3, and atrogin-1 after 4 weeks of eccentric endurance exercise may inhibit muscle atrophy, and then ameliorate metabolic disorders and increase insulin sensitivity in type 2 diabetes.

Key words: eccentric endurance exercise, type 2 diabetes, rat, muscle atrophy, myostatin

王继, 周越, 张荷, 李文博, 黄怡. Myostatin信号通路在4周离心耐力运动改善2型糖尿病大鼠骨骼肌萎缩中的作用[J]. 中国应用生理学杂志, 2018, 34(3): 223-228.

WANG Ji, ZHOU Yue, ZHANG He, LI Wen-bo, HUANG Yi. The role of myostatin signaling pathway in improvement of skeletal muscle atrophy in type 2 diabetic rats after 4 weeks of eccentric endurance exercise[J]. CJAP, 2018, 34(3): 223-228.

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Myostatin信号通路在4周离心耐力运动改善2型糖尿病大鼠骨骼肌萎缩中的作用

The role of myostatin signaling pathway in improvement of skeletal muscle atrophy in type 2 diabetic rats after 4 weeks of eccentric endurance exercise

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