| Objective: To investigate the effects of perindopril with spironolactone on myocardial fibrosis and expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase 2(MMP-2) in renovascular hypertensive(RH)rats.Methods: I begin my research by using the folling methods: RH models were established by the two-kidney-one-clip technique in thirty two healthy male wistar rats, weight 200±20g,which were randomly divided into RH group, Perindopril group and perindopril add spironolactone group(combination group) and sham group. After four weeks, rats in perindopril group were administered perindopril 2mg/kg.d-1 and combination group were administered perindopril 2mg/kg.d-1 add spironolactone 20mg/kg.d-1. Rats in sham group and RH group were administered with the same quantity of distilled water for eight weeks. Systolic blood pressure(SBP) of rats tail artery was measured at before oprating, the end of four weeks and twelve weeks. At the end of twelve weeks we killed the rats cutting left ventricular tissue into two parts. We use one of the part to check Hydroproline concentration(HC) according the directions of the HC. Collagen volume fraction(CVF), perivascular collagen area(PVCA) , the expression of transforming growth factor-β1(TGF-β1)and matrix metalloproteinase 2 in left ventricular tissue were calculated by Immunohistochemistry and medical image analysis system BI-2000. Content of antigen was measured by gray scale.The lower of gray scale ,the stronger of content of antigen.Serum potsssium was measured by automatic biomedical analysator.heart hypertrophy was measured by weight of heart index.Results: 1. SBP: Compared with the sham group,at the end of four weeks,SBP in RH group,Perindopril group and combination group were remarkedly rising(P<0.01). SBP among RH group, Perindopril group and combination group has no statistic difference. At the end of twelve weeks, SBP in Perindopril group and combination group were remakedly decreasing(P<0.01), but still higher than sham group(P<0.01). SBP between Perindopril group and combination group has no stastic difference. 2. Weight of heart index: Compared with the sham group, weight of heart index in RH group were remarkedly rising(P<0.01). Weight of heart index in Perindopril group and combination group were also obvious rising(P<0.05). Weight of heart index in Perindopril group and combination group has no stastic difference. Compared with the RH group, weight of heart index in Perindopril group and combination group were decreasing(P<0.05). 3. CVP,PVCA and HC: Compared with RH group, CVF,PVCA and HC in combination group were remarkedly decreasing(P<0.01). CVFand PVCA in Perindopril group were remarkedly decreasing(P<0.01). HC were decreasing(P<0.05).Compared with the Perindopril group, CVP and HC in combination group were obvious decreasing(P<0.01), PVCA in combination group were decreasing(P<0.05). CVF and PVCA in sham group and combination group has no stastic difference. 4.The expression of MMP-2 and TGF-β1: Compared with RH group,the expression of MMP-2 and TGF-β1 in sham group, Perindopril group and combination group were remarkedly decreasing(P<0.01), Compared with the perindopril group, the expression of MMP-2 and TGF-β1 in combination group were decreasing(P<0.05). The expression of MMP-2 and TGF-β1 in sham group and combination group has no stastic difference. 5.The results of Van Gieson by pathology: Staining of perivascular collagen fiber in sham group are salmon pink, discontinuity. Staining of Perivascular collagen fiber in Perindopril group are red, continuity. Staining of Perivascular collagen fiber in renovascular hypertensive group are cardinal red, circularity. 6. Immuno-histochemistry staining of MMP-2 and TGF-β1:. Sham group: there are small brown particle in cardiac muscle cytoplasm, divergence, weakly positive. Renovascular hypertensive group:there are more brown particles in cardiac muscle cytoplasm, divergence. Perindopril group: there are moderately tiny brown particles in cardiac muscle cytoplasm, divergence.Combination group: there are small tiny brown particles in cardiac muscle cytoplasm, divergence, positive.Conclusion:①SBP,CVP,PVCA and HC in RH group were remarkedly rising ,it means that renovascular hypertension connect closely with myocardial fibrosis.②MMP-2 and TGF-β1 play an important role in renovascular hypertensive rat myocardial fibrosis forming. The level of MMP-2 and TGF-β1 in four group: RH group>Perindopril group >combination group>sham group. MMP-2 and TGF-β1 are positive correlation.③Perindopril and perindopril add spironolactone can lower RH rat hypertesion ,and educe blood pressure dependencing inhibiting myocardial fibrosis.④Perindopril can inhibit progress of RH rat myocardial fibrosis by inhibiting the expression of MMP-2 and TGF-β1.⑤perindopril add spironolactone can remarkedly inhibit progress of RH rat myocardial fibrosis than perindopril.this changing is at the same condition without any connecting with blood pressure .the mechanism may be combination drug can remarkedly inhibit the expression of MMP-2 and TGF-β1.
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