罗格列酮对糖尿病大鼠心肌损害防护作用的机制研究  

Protective effect and mechanism of Rosiglitazone on myocardial injury in diabetic rats

作　　者：张晓菲 杨景[2] 张忠辉[3] 

机构地区：[1]重庆沙坪坝人口与计划生育生殖健康中心,重庆400030 [2]第三军医大学西南医院病理学研究所,重庆400038 [3]第三军医大学西南医院内分泌科,重庆400038

出　　处：《中国现代医学杂志》2012年第11期14-19,共6页China Journal of Modern Medicine

基　　金：国家"十一五"攻关项目(No:2006BA702B01)

摘　　要：目的探讨罗格列酮对糖尿病大鼠心肌损害防护作用的机制。方法用链脲佐菌素(STZ)将39只10周龄雄性Wistar大鼠诱导成糖尿病大鼠模型,分为胰岛素治疗组、罗格列酮治疗组及未治疗组(每组13只),并以13只正常大鼠作对照。于第16周末抽取各组大鼠心脏血测定TNF-α、IL-6、C-反应蛋白、SOD及P物质水平,并处死取心脏进行病理学观察;用免疫组织化学染色观察心肌中晚期糖基化终末产物(AGEs)与过氧化物酶体增殖物激活受体-γ(PPAR-γ)含量的变化。结果未治疗对照组血清IL-6、TNF-α、C-反应蛋白水平均明显高于正常对照组(P<0.05),胰岛素治疗组和罗格列酮治疗组与正常对照组比较无差异;未治疗对照组血清SOD、P-物质水平与正常对照组相比明显降低(P<0.01),胰岛素治疗组和罗格列酮治疗组的SOD和P-物质显著高于未治疗对照组(P<0.01,P<0.05)。组织学观察:未治疗对照组部分心肌细胞肥大、玻璃样变;心肌间质纤维组织增生,不规则分隔心肌细胞;胰岛素治疗组和罗格列酮治疗组未出现明显的组织学改变。免疫组织化学显示,AGEs蛋白、PPAR-γ蛋白均呈棕黄色颗粒状,弥漫或斑片状沉积于心肌细胞胞浆中;在未治疗对照组AGEs最高,PPAR-γ最低。结论糖尿病大鼠受损的心肌中AGEs蓄积和血清炎症因子增高,罗格列酮与胰岛素一样对糖尿病大鼠心肌损害具有防护作用。【Objective】 To study the protective effect of Rosiglitazone on cardiac muscle damage in diabetic rats.【Methods】 The rats were divided into normal control group（C group,n =13）,diabetic control group（DC group,n =13）,diabetes and insulin treatment group（D I group,n =13）,diabetes and Rosiglitazone treatment group（DR group,n =13）.The diabetic rat models were established with high fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg streptozotocin injection,the rats were identified as diabetic when their fasting blood glucose（FBG） over 7.0 mmol/L.The living rats were given corresponding treatment,subcutaneous injection of 1 to 2 U/d insulin,intragastric injection of 5 mg/（kg·d） Rosiglitazone,or sterile water.Heart blood samp les of rats from each group were collected to measure TNF-α,IL-6,C-RP,SOD and P material levels in the 16th weekend.Also the Myocardium was taken for pathological observation.Use of chemical stain to see the myocardium was poorly organized in the AGEs and PPAR-gamma content changes.【Results】 The levels of IL-6,TNF-α and C-RP of all the diabetic model groups were significantly higher than those of the normal group（P 0.05）,No difference was observed in DI and DR groups compared with the normal control group;the SOD and SP level in diabetic group was significantly lower than that in the normal group（P 0.01）,the SOD and SP levels were significantly increased in insulin and Rosiglitazone groups compared with Diabetes Group（P 0.01,P 0.05）.Organization to observe： Diabetes group of the myocardium large,Glass of them became;Myocardium stroma fiber organization growths,irregular Separate From cardiac muscle cells;Insulin and Rosiglitazone in groups not appear of the organization to change.Immunohistochemistry showed that AGEs protein,PPAR-γ protein showed a brown granular,Diffuse or patchy deposition in the cytoplasm of myocardial cells,AGE in the diabetic group the highest,PPAR-γ minimum.【Conclusion】 Diabetes,AGEs accumulate in th

关 键 词：糖尿病 2型 糖基化终末产物 高级 过氧化物酶体增殖物激活受体-γ(PPAR-γ) 疾病模型 动物 心肌病理 胰岛素 罗格列酮 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]