糖尿病大鼠心肌纤维化与心肌AGEs/RAGE水平的变化  

Changes of myocardial fibrosis and AGEs/RAGE levels in diabetic rats

作　　者：侯改霞[1] 肖国强[2] 习雪峰[1] 刘倩倩[1] HOU Gaixia;XIAO Guoqiang;XI Xuefeng;LIU Qianqian(School of Physical Education,Henan University,Kaifeng 475001,China;School of Physical Education,South China Normal University,Guangzhou 510006)

机构地区：[1]河南大学体育学院,河南开封475001 [2]华南师范大学体育科学学院,广州510006

出　　处：《中国实验动物学报》2018年第4期461-466,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：河南省教育厅科学技术研究重点项目(No.14B890010)~~

摘　　要：目的通过构建Ⅱ型糖尿病大鼠模型,研究该模型心肌纤维化和心肌AGEs/RAGE水平的变化情况。方法雄性SD大鼠高脂饲料饲喂6周后,过夜空腹12 h,腹腔注射小剂量链脲佐菌素(STZ,30 mg/kg)。注射3、7 d后检测大鼠随机血糖浓度,两次随机血糖≥16.7 mmol/L为Ⅱ型糖尿病大鼠建模成功。在建模成功后第4、8和12周,检测大鼠血FBG、insulin和左心室AGEs、Hyp含量及Masson染色、RAGE表达的变化。结果造模成功后第4、8和12周,糖尿病对照组(4D,8D,12D)血FBG水平均较同周次正常对照组(4C,8C,12C)显著升高,体重显著下降;造模成功后第12周时,糖尿病对照组(12D)大鼠Insulin显著高于同周次正常对照组(12C)和4周时糖尿病对照组(4D);从造模成功后第8周开始,糖尿病对照组(8D,12D)心肌Hyp、CVF、AGEs和RAGE与正常对照组(8C,12C)相比均显著升高;2型糖尿病大鼠心肌AGEs/RAGE水平与CVF呈显著正相关。结论高脂饮食饲喂加腹腔注射小剂量STZ,能够成功复制Ⅱ型糖尿病大鼠模型。随着病程的延长,心肌纤维化和心肌AGEs含量、RAGE蛋白表达均呈逐渐上升趋势,且Ⅱ型糖尿病大鼠心肌AGEs/RAGE水平与心肌纤维化存在有正相关关系。Objective To established a rat model for type II diabetes and to investigate the gradual changes of myocardial fibrosis and myocardial AGEs/RAGE levels in type II diabetes. Methods Male SD rats were fed high-fat fodder for 6 weeks,and then injected a small dose of streptozotocin（ STZ,30 mg/kg） after overnight fasting for 12 h. The random blood GLU was detected on the 3 thand 7 thdays,respectively,after STZ injection. The rats with random blood GLU concentration higher or equal to 16. 7 mmol/L detected twice were considered as successful rat model of type II diabetes.Six rats of group C and six rats of group D fasting for 12 h were killed after intraperitoneal anesthesia at the 4^（th）,8^（th） and 12^（th） weeks after the successful establishment of type II diabetes models. Blood samples were taken for FBG and insulin detection. A portion of the left ventricle tissue was used for Masson staining and immunohistochemical detection of RAGE,and the other portion of the left ventricle was used for the detection of content of AGEs and Hyp. Results The FBG levels of group D were significantly higher,and the body weights of group D were significantly lower than group C at the same weeks. Blood insulin of the group D at the 12^（th） week was significantly higher than that of the group C at the 12^（th） week and group D at the 4^（th） week. Myocardial Hyp,CVF,AGEs and RAGE of group D were significantly higher than those of the group C at the 8^（th）,12^（th） weeks. The AGEs/RAGE level of myocardium in the diabetic rats was positively correlated withCVF. Conclusions The model of type II diabetes is successfully established through intraperitoneal injecting a low-dose streptozotocin to SD rats which had been fed high-fat fodder. The rat models of type II diabetes demonstrate myocardial fibrosis at the 12^（th） week after the successful establishment of diabetes. With the further development of diabetes,the myocardial fibrosis,content of myocardial AGEs,RAGE protein expression of the diabetic rat

关 键 词：高脂饮食 链脲佐菌素 Ⅱ型糖尿病 心肌纤维化 AGEs/RAGE SD大鼠 

分 类 号：Q95-33[生物学—动物学]