胰岛素样生长因子-1对糖尿病大鼠心肌保护作用的探讨  

Effects of insulin-like growth factor-1 on the myocardium in diabetic rats

作　　者：李静波[1] 林静娜[1] 宋轶萱[1] 相莉[1] 毋中明[2] 

机构地区：[1]天津市人民医院内分泌科,300121 [2]天津医科大学代谢病医院基础医学研究所

出　　处：《中华医学杂志》2014年第42期3329-3333,共5页National Medical Journal of China

基　　金：天津市卫生局科技基金（2010KZ45）

摘　　要：目的 观察胰岛素样生长因子-1（IGF-1）对糖尿病大鼠心肌纤维化及心肌细胞凋亡的影响,探讨其对糖尿病心肌病的保护作用.方法 大鼠尾静脉注射链脲佐菌素建立糖尿病模型,随机分为糖尿病组、胰岛素治疗组及IGF-1治疗组,同时设立正常对照组.干预10周处死大鼠测定心重指数、血清胰岛素和IGF-1水平.取部分左心室组织HE染色及Masson染色,末端标记法（TUNEL）检测心肌细胞凋亡,免疫组织化学及免疫印迹（Western blot）检测大鼠心肌组织IGF-1受体（IGF-1R）水平.结果 IGF-1及胰岛素治疗后大鼠心重指数较糖尿病组明显降低.与正常对照组相比,糖尿病组血清IGF-1水平明显下降,IGF-1治疗组血清IGF-1水平明显升高.HE及Masson染色结果显示,与正常对照组比较糖尿病大鼠出现心肌组织病变,IGF-1及胰岛素治疗后大鼠心肌组织病变情况明显改善.TUNEL结果显示IGF-1及胰岛素治疗组心肌细胞凋亡指数较糖尿病模型组明显下降.糖尿病大鼠心肌组织中IGF-1R水平较正常对照组明显增加,IGF-1治疗组较糖尿病模型组明显减低,胰岛素治疗组IGF-1R水平较糖尿病模型组无明显变化.结论 IGF-1治疗能够改善心肌间质纤维化及抑制心肌细胞凋亡,对糖尿病心肌病有治疗作用.Objective To observe the effects of insulin-like growth factor-1 （IGF-1） on myocardial fibrosis and myocardial cell apoptosis in diabetic rats,so as to clarify the potential benefit of IGF-1 on diabetic cardiomyopathy.Methods Diabetic rats were induced by caudal injection of STZ,and the diabetic rats were randomly divided into 3 groups：diabetes group,the insulin treatment group and the IGF-1 treatment group.Normal control（NC） group did not receive any therapy.The experiment lasted 10 weeks and the heart weight was recorded to calculate the heart weight index.The serum insulin and IGF-1 level were determined.HE staining and Masson staining were taken on the left ventricular tissue.The cardiomyocyte apoptosis were measured by methods of terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL）,the expression levels of IGF-1 R in cardiomyocytes were measured by immunohistochemical and Western blot.Results Compared with diabetes group,the heart weight index of the insulin treatment group and the IGF-1 treatment group were significantly decreased.Serum levels of IGF-1 in diabetes group were significantly decreased compared with NC group,and the levels were significantly increased in IGF-1 treatment group.The results of HE and Masson staining showed that compared with NC group,diabetes rats＇ myocardial tissue were damaged.Myocardial tissue pathological changes of rats were significantly improved after insulin and IGF-1 treatment.The result of TUNEL indicant cardiomyocyte apoptosis index in diabetes group was obviously increased than the NC group,and that in IGF-1 treatment group were decreased compared with diabetes group.IGF-1R levels in diabetic rats myocardial tissue were rised than the NC group,it was declined in IGF-1 treatment group,but in insulin treatment group the levels had no obvious change.Conclusions IGF-1 can inhibite the myocardial fibrosis and cardiomyocyte apoptosis.It maybe have the possible effect on the treatment of diabetic cardiomyopathy.

关 键 词：糖尿病 心肌病 胰岛素样生长因子-1 纤维化 凋亡 

分 类 号：R542.2[医药卫生—心血管疾病] R587.2[医药卫生—内科学]