曲尼司特对糖尿病大鼠心肌纤维化的作用

目的探讨曲尼司特对糖尿病大鼠心肌纤维化的作用及其可能机制。方法健康♂SD大鼠一次性尾静脉注射链脲佐菌素制备糖尿病大鼠模型,随机分为糖尿病组(DM组),曲尼司特低剂量组(Tra1)及高剂量组(Tra2),造模成功72 h后每天ig给予曲尼司特100 mg.kg-1.d-1及200 mg.kg-1.d-1,同时设立对照组(NC组)。饲养12周。测量血糖、心脏质量指数、血浆及心肌血管紧张素Ⅱ水平;Masson染色观察心脏形态学变化,免疫组化法和Western印迹法检测心肌组织CTGF、Ⅰ型、Ⅲ型胶原蛋白表达。结果①与NC组相比,DM组大鼠心脏质量指数、血浆及心肌血管紧张素Ⅱ(AngⅡ)水平明显升高(P<0.01),心肌间质纤维化明显,心肌CTGF蛋白、Ⅰ型、Ⅲ型胶原蛋白表达增加;②与DM组比较,Tra1、Tra2组大鼠心脏质量指数、血浆及心肌AngⅡ水平均明显下降(P<0.05),心肌间质纤维化减轻,心肌CTGF、Ⅰ型、Ⅲ型胶原蛋白表达减少。结论曲尼司特能降低糖尿病大鼠心肌AngⅡ水平,减少CTGF、Ⅰ型、Ⅲ型胶原蛋白的表达,从而抑制糖尿病大鼠心肌纤维化。

Effects of tranilast on myocardial fibrosis of diabetic rats

Aim To study the role of tranilast in myocardial fibrosis of the diabetic rats and its possible mechanism.Method Diabetic rat models were induced by intraperitoneal injection of streptozotocin(STZ) in SD rats.The rats were randomly divided into diabetes group and tranilast treatment groups(low dose group,high dose group).In the low tranilast treatment group(Tral) and high group(Tra2),the rats were given intravenous injection of tranilast(100 mg·kg-1·d-1 and 200 mg·kg-1·d-1) daily respectively,72h after the models were established.Normal control group was also established at the same time.After 12 weeks,the blood sugar,heart quality index,plasma and the myocardial angiotensin Ⅱ(Ang Ⅱ) level were detected.MASSON staining was used to observe the heart morphological changes.Immunohistochemical method and Western blotting method were used to detect myocardial tissue CTGF,collagen Ⅰ,Ⅲ protein expression.Results ① Compared with normal control group,the heart quality index,plasma and myocardial angiotensin Ⅱ level were higher in diabetes group(P<0.05).The myocardial fibrosis of diabetic rats was obvious,myocardial CTGF protein,collagen Ⅰ,Ⅲ expression were increased.② Compared with diabetes group,the heart quality index、plasma and myocardial angiotensin Ⅱ level were lower in tranilast treatment group(P<0.05).The myocardial fibrosis reduced,myocardial CTGF protein、 collagen Ⅰ,Ⅲ expression were reduced.Conclusion Tranilast can reduce diabetic rats myocardial Ang Ⅱ content,collagenⅠ,Ⅲ and CTGF protein expression,consequently inhibit diabetic myocardial fibrosis.