Effects of benazepril on expression of matrix metalloproteinase and transforming growth factors in myocardial extracellular matrix remodeling of diabetic rats

OBJECTIVE To study the mechanism of benazepril(BZ) on myocardial extracellular matrix remodeling of diabetic rats.METHODS Diabetic animal models were induced by injecting streptozotocin into Spraque-Dawley rats.BZ 10 mg·kg-1 was ip given to rats in BZ group,once daily,for 12 weeks.The left ventricular myocardium was observed with the light microscope and electronmicroscope.Heart mass indexes were detected.Collagen typeⅠ and typeⅢ,matrix metalloproteinases(MMP-2),tissue inhibitor of metalloproteinases(TIMP-2),transforming growth factor-β1(TGF-β1) and connective tissue growth factor(CTGF) were detected by Western blotting.RESULTS Compared with normal control group,the heart mass indexes and the expression of collagen typeⅠ and typeⅢ were higher in diabetes group(P0.05).TIMP-2 protein in diabetes group were significantly higher while the expression of MMP-2 was significantly lower(P0.01).The expression of TGF-β1 and CTGF was obviously strengthened(P0.05).Myocardial interstitial fibrosis occurred in diabetic rats.After benazepril was used for 12 weeks,compared with diabetes group,the heart mass indexes obviously decreased from(4.13±0.18)mg·g-1 to(3.42±0.13)mg·g-1.The expression of collagen typeⅠ and typeⅢ was lower(P0.05).The expression of MMP-2 increased,the expression TIMP-2 decreased(P0.05),and the expression of TGF-β1 and CTGF was degraded significantly(P0.05).Myocardial interstitial fibrosis was also lessened.Compared with normal control group,MMP-2 expression decreased,but the expression of TIMP-2 and CTGF still increased in BZ group.CONCLUSION BZ could inhibit the myocardial interstitial fibrosis of diabetic rats,improve myocardial extracellular matrix remodeling by inhibiting of TGF-β1 and CTGF expression and upregulating MMP-2 expression.