摘要
目的通过研究卡托普利、贝那普利、福辛普利对糖尿病大鼠心肌转化生长因子β1(TGF-β1)及基质金属蛋白酶(MMPs)的影响,探讨这3种药物对糖尿病大鼠心肌的抗纤维化作用。方法50只SD大鼠分为10只正常组,40只糖尿病组,糖尿病组链脲佐菌素注射建模。建模成功后将成功的糖尿病鼠(37只,未成功2只,死亡1只)随机分糖尿病组(n=9)、卡托普利治疗组(n=9)、贝拉普利治疗组(n=9)、福辛普利治疗组(n=10),免疫组化法测Ⅰ、Ⅲ型胶原的表达,TGF-β1、基质金属蛋白酶特异性抑制物(TIMP-1)和MMP-1蛋白的表达,RT-PCR法测TIMP-1和MMP-1mRNA的表达。结果糖尿病组心脏指数心室指数显著大于正常组(P<0.05),Ⅰ、Ⅲ型胶原的表达也增加(P<0.05),存在着心肌间质纤维化,胶原1、胶原Ⅲ、TGF-β1、TIMP-1蛋白及TIMP-1 mRNA的表达增高(P<0.05),MMP-1蛋白及mRNA的表达减少(P<0.05)。经过卡托普利、福辛普利、贝那普利后,上述各异常指标均有所改善。结论3组药物通过对TGF-β1和MMPs的影响可明显改善糖尿病心肌间质纤维化。卡托普利的疗效比贝那普利与福辛普利稍差,贝那普利与福辛普利之间无差异。
Objective To investigate the effect of captopfil, benazepri and fosinopril on TGF-β1 and MMPs so as to improve myocardial interstitial fibrosis of diabetic rats. Methods 50 male SD rats were randomly divided into two groups, 10 rats was in normal control group and the others were in asstreptozotocin（STZ） induced group. The diabetes mellitus models were successfully induced in 38 rats, then they were divided into diabetic control group, captopril treatment group, benazepri treatment group and fosinopril treatment group. Immunohistochemistry was used to measure the levels of type Ⅰ collagen, type Ⅲ collagen, TGF-β1 protein, MMP-1 and TIMP-1 protein. The mRNA of MMP-1 and TIMP-1 mRNA were measured by RT-PCR. Results At the end of the experiment, the cardiac index and the ventricle index were significantly higher in DM group than those in normal control group（ P 〈 0.05 ）. The expressions of type Ⅰ, type Ⅲ collagen, TGF-β1 protein,TIMP-1 protein and mRNA were also significantly higher than those in normal control group, however,the expression of MMP-1 protein and mRNA were significantly lower. All the indexes were greatly improved in treatment groups, as compared with those in DM group. Conclusion The three drugs can improve obviously the myocardial interstitial fibrosis in diabetic rats by decreasing the expression of Ang Ⅱ, further affecting the expression of TGF-β1, MMP-1 and TIMP-1. The therapeutic effect of captopril is a little inferiorer than that of the other drugs. There is no significant difference in the therapeutic effect between benazepri treatment group and fosinopril treatment group.
出处
《河北医药》
CAS
2010年第1期16-18,共3页
Hebei Medical Journal
基金
湖北省医学科学研究重点课题计划项目(编号:JX2A19)
关键词
血管紧张素转换酶抑制剂
糖尿病心肌病
心肌间质纤维化
转化生长因子-Β1
基质金属蛋白酶
angiotensin-converting enzyme inhibitor
diabetic cardiomyopathy
myocardial interstitial fibrosis
transforming growth factor beta 1
matrix metalloproteinases
