Apelin-13对糖尿病大鼠相关肌少症的作用机制探讨

The effect and mechanism of apelin-13 on diabetes-associated sarcopenia in rats

目的观察apelin-13对糖尿病相关性肌少症大鼠的作用并探讨其可能机制。方法高脂饲料喂养雄性自发性2型糖尿病Goto-Kakizaki大鼠建立糖尿病相关肌少症大鼠模型,同时每天给大鼠腹腔注射apelin-13(0.1μmol/kg),实验时间为12周;Wistar大鼠作为对照组,每天腹腔注射等量的生理盐水。测量大鼠的饮水量摄食量和体重,同时检测大鼠的空腹血糖、空腹胰岛素和血脂水平,计算胰岛素抵抗指数,称量大鼠腓肠肌的湿重,观察腓肠肌形态学改变;Westernblot检测腓肠肌中磷脂酰肌醇3激酶(PI3K)和磷酸化Akt(p-Akt)蛋白的表达。结果与模型组比较,模型+apelin-13组大鼠的饮水量在第8和12周均显著降低(F=7.17.7.91),摄食量(F=5.84、6.12)和体重(F=5.76、6.07)在第8和12周均显著增加(均P<0.05),空腹血糖水平在第8和12周均显著降低(F=8.07.8.24,均P<0.05),血清三酰甘油、总胆固阵、低密度脂蛋白胆固醇、高密度脂蛋白胆固鹳空腹胰岛紫水平和胰岛素抵抗指数第12禺均显著降低(F-5.17.7.94.10.27、8.32.6.94、11.31,均P<0.05),大鼠脖肠肌的湿重显蓉增加[(0.63±0.04)g比(1.02±0.05)g,t=4.32、P<0.05]。与模型组比较,模型+apelin-13组大鼠腓肠肌中PI3K和p-Akt蛋白表达均显著上调(t=7.32、8.07,均P<0.05)。结论Apelin-13对糖尿病相关肌少症具有抑制作用,其机制可能与上调骨骼肌中PI3K和p-Akt的表达有关。

Objective To observe the effect of Apelin-13 on diabetes-related sarcopenia in rats model and explore the underlying mechanism.Methods This experiments were divided into 3 groups.In the normal control group,Wistar rats were fed by ordinary feed,intraperitoneally injected daily with the equal amount of normal saline.In the model+control group,diabetic-related sarcopenia model was established in rats with fat-fed Goto-Kakizaki rats for 12 weeks and intraperitoneally injected daily with the equal amount of normal saline.In the model+apelin-13 group,apelin-13(0.1 mol/kg)was intraperitoneally injected into diabetic-related sarcopenia model daily for 12 weeks.The water intake,food intake,and body weight were measured.The fasting blood glucose,fasting insulin and blood lipid levels of rats were measured,and the insulin resistance index was calculated.The wet weight of the rats'gastrocnemius muscle was weighed,and the morphological changes of the gastrocnemius muscle were observed.Western blot was used to detect the protein expressions of phosphatidylinositol-3 kinase(PI3K)and phosphorylated Akt(p-Akt)in the gastrocnemius muscle of rats.Results Compared with the model+normal saline group,the model+apelin-13 group showed that the following parameters were significantly improved.(1)The water intake of rats was significantly decreased at 8,and 12 weeks(F=7.17 and 7.91),and food intake was significantly decreased(F=5.84 and 6.12)and body weight were significantly increased at 8 and 12 weeks(F=5.76 and 6.07)(all P<0.05).(2)The levels of fasting blood glucose were significantly decreased at 8 and 12 weeks(F=8.07 and 8.24,all P<0.05).(3)Serum triglycerides,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,the levels fasting insulin and the insulin resistance index were significantly decreased at week 12 (F=5.17,7.94,10.27,8.32,6.94 and 11.31,all P<0.05);(4)The wet weight of gastrocnemius muscle was significantly increased(0.63±0.04 g and 1.02±0.05 g,t=4.32,P<0.05).(5)Compared with the model+normal saline group,the model+apelin-13 group showed the protein expressions of PI3K and p-Akt in the gastrocnemius muscle of rats were significantly up-regulated(t=7.32,8.07,both P<0.05).Conclusions Apelin-13 has an inhibitory effect on diabetes-related sarcopenia,and its mechanism may be related to the up-regulation of PI3K and p-Akt expression in skeletal muscle.