维生素D对2型糖尿病大鼠糖脂代谢及骨骼肌组织中哺乳动物雷帕霉素靶蛋白、固醇调节元件结合蛋白1c、成肌分化抗原表达影响的研究

Effects of vitamin D on glucose and lipid metabolism and expression of mTOR,SREBP-1c and MyoD in skeletal muscle tissue of type 2 diabetic rat model

目的探讨维生素D(VitD)对T2DM大鼠糖脂代谢及骨骼肌组织中雷帕霉素靶蛋白(m TOR)、固醇调节元件结合蛋白1c(SREBP-1c)、成肌分化抗原(MyoD)mRNA表达的影响。方法82只8周龄SD大鼠随机选取10只为正常对照(NC)组,其余72只给予高脂、高胆固醇饲料喂养+腹腔注射STZ建模,成功60只,分为T2DM组、VitD干预组(T2DM+CMM-VitD)、激动剂组(T2DM+L-leucine)、抑制剂组(T2DM+rapamycin)、VitD干预激动剂组(T2DM+CMM-VitD+L-leucine)、VitD干预抑制剂组(T2DM+CMM-VitD+rapamycin),每组各10只。给药第12周末收集生化指标,RT-PCR检测肌肉组织中mTOR、SREBP-1c、MyoD mRNA表达。结果与T2DM组比较,T2DM+CMM-VitD、T2DM+rapamycin、T2DM+CMM-VitD+rapamycin组FPG、TG、TC、LDL-C降低(P<0.05),HDL-C升高(P<0.05),T2DM+L-leucine组FPG、LDL-C升高,HDL-C降低(P<0.05),T2DM+CMM-VitD+L-leucine组FPG、TG、TC、LDL-C降低(P<0.05)。与T2DM组比较,T2DM+CMM-VitD、T2DM+rapamycin、T2DM+CMM-VitD+rapamycin组mTOR、SREBP-1c mRNA表达降低(P<0.05),MyoD mRNA表达升高(P<0.05)。Spearman相关分析显示,MyoD与HDL-C呈正相关(P<0.05),与mTOR、SREBP-1c、TG、LDL-C呈负相关(P<0.05)。结论VitD可增加肌量,其机制可能是通过下调肌肉组织中mTOR、SREBP-1c mRNA表达和上调MyoD mRNA表达实现。

Objective To investigate the effects of vitamin D on glucose and lipid metabolism and mRNA expression of mTOR,SREBP-1C and MyoD in skeletalmuscle tissue of type 2 diabetic rats.Methods A total of 82 SD rats at the age of 8 weeks were enrolled in this study.10 rats were randomly selected as normal control(NC)group,and the other 72 rats were treated with high fat and cholesterol feed feeding plus intraperitoneal injection STZ to establish diabetic model.The model was successfully established in 60 rats.Then the 60 rats were divided into six groups with 10 rats per group:T2DM group,T2DM+CMM-VitD group,T2DM+L-leucine group,T2DM+rapamycin group,T2DM+CMM-VitD+L-leucine group,T2DM+CMM-VitD+rapamycin group.Biochemical parameters were collected and the expressions of mTOR,SREBP-1c and MyoD mRNA in rat muscle tissue were determined by Real-time PCR at the end of the 12 th week of intervention.Results Compared with T2DM group,FPG,TG,TC,and LDL-C decreased,while HDL-C increased in T2DM+CMM-VitD group,T2DM+rapamycin group and T2DM+CMM-VitD+rapamycin group.Compared with T2DM group,FPG and LDL-C increased,while HDL-C decreased in T2DM+L-leucine group(P<0.05),FPG,TG,TC,and LDL-C decreased in T2DM+CMM-VitD+L-leucin group(P<0.05).Compared with T2DM group,mTOR and SREBP-1c mRNA expression decreased(P<0.05),while MyoD mRNA expression increased(P<0.05)in T2DM+CMM-VitD,T2DM+rapamycin,T2DM+CMM-VitD+rapamycin group.Spearman correlation analysis showed that MyoD was negatively correlated with mTOR,SREBP-1c,TG,LDL-C(P<0.05),and positively correlated with HDL-C(P<0.05).Conclusion VitD may down-regulate the expression of mTOR and SREBP-1c mRNA and up-regulate the expression of MyoD mRNA in muscle tissue to increase muscle mass.