参芪复方介导IGF-1/PI3K/Akt通路干预糖尿病大鼠骨骼肌病变的实验研究

Experiment of Shenqi Compound Recipe Mediating IGF-1/PI3K/Akt Intervening Skeletal Muscle of Mice with Type 2 Diabetes Mellitus

目的：观察参芪复方对2型糖尿病大鼠骨骼肌的保护作用及其分子机制探索。方法：GK大鼠40只,随机分为模型组、参芪复方组及西格列汀组,另设Wistar大鼠10只作为正常对照组。除正常对照组给予普通饮食外,其余各组给予高脂饮食,连续8周,建立2型糖尿病模型。造模同时开始分组给药,期间监测动物一般情况及血糖水平,试验结束后腹主动脉采血,分离血清,检测IGF-1含量,取腓肠肌称取湿重及观察其病理形态学改变,Western blot法检测腓肠肌PI3K,Akt及p70s6k蛋白表达水平。结果：与正常对照组相比,模型组大鼠腓肠肌湿重、IGF-1、PI3K、Akt以及p70s6k明显降低（P〈0.05）,且病理观察发现腓肠肌细胞萎缩,有较大面积水肿,肌间淋巴细胞浸润。经参芪复方治疗后,GK大鼠腓肠肌湿重、IGF-1、PI3K、Akt以及p70s6k均有明显升高,差异有统计学意义（P〈0.05）,且病理观察未见明显肌细胞萎缩、水肿,炎细胞浸润少。结论：参芪复方对糖尿病骨骼肌有保护作用,其可能的机制是激活IGF-1/PI3K/Akt蛋白质合成代谢相关通路。

Objective： To observe the effect of Shenqi Compound Recipe on the protective effect for skeletal muscle of mice with type 2 diabetes mellitus and explore the possible molecular mechanism. Methods： 40 GK mice were randomly divided into the three groups： the model group,the Shenqi Compound Recipe group and the Sitagliptin group. Another 10 Wistar mice were assigned to the normal group. All the GK mice were fed by high fat food for 8 weeks,whereas Wistar mice were fed by normal food for the same time period. Investigational products were given to animals according to groups assigned at the start of molding. General condition and blood glucose were monitored during the study. Blood samples were withdrawn from abdominal aorta to evaluate the level of IGF-1. Gastrocnemius muscle were collected,wet weight measured and histopathologic change observed under microscope.Western blot method was used to assess the protein expression of PI3 K,Akt as well as p70 s6 k in muscle tissue. Results： Compared with normal group,the following indexes of model group mice were decreased dramatically（P〈0. 05） ： wet weight of gastrocnemius muscle,IGF-1,PI3 K,Akt and p70 s6 k. Muscle cell atrophy,large scale of edema and lymphocytes infiltration were observed under the microscope. After treatment of Shenqi Compound Recipe,wet weight of gastrocnemius muscle,IGF-1,PI3 K,Akt and p70 s6 k increased significantly（P〈0. 05）. No obvious muscle cell atrophy or edema was noticed,and the inflammation infiltration was mild. Conclusion： Shenqi Compound Recipe could protect skeletal muscle of type 2 diabetes mellitus mice. The possible mechanism was that it might stimulate IGF-1/PI3 K/Akt protein anabolic metabolism related signal pathway.