Efficacy Of RAS Inhibitor For SHR In BMP-7/Smads Expression

IntroductionThe natural history of myocardial fibrotic remodeling is characterized by a gradual worsening with time.This type of chang was demominated strutural remodeling.However,up today little is known about the underling structural remodeling mechanism.Previous studies have shown that reni-angiotensin system(RAS) play a ricular remodeling role in the vent.To explore the effects of Telmisartan and eplerenon on myocardical fibrotic remodeling and involvement of bone morphogenetic protein-7 (BMP-7)and Smad2,3expression.Materials and Methods1. Materials(1) speimanTwenty-six male SHR were randomly divided in 4 groups:Telmisartan group eplerenon group,telmisartan and eplerenon group and comparative group. Telmisartan group were poured telmisartan (10mg·kg-1·d-1);Eplerenon group were poured eplerenon (100mg·kg-1·d-1); Telmisartan and eplerenon group were poured telmisartan (5mg-kg-1·d-1) and eplerenon (50mg·kg-1·d-1)Comparative group were poured dimethyl sulfoxide (lml·d-1)in stomach(2) Main agents,equipment and sourceAntibody of BMP-7,Smad2,3,collagen I from BOSHIDE biological technology company in Beijing.Thermo Fish scientific Lab Vision Autostainer 480. 2.Methods (1)Before,after 2weeks and 8 weeks treatment,the blood pressure were measured by tail-sleeve method..After week 8,the protein levels of BMP-7,Smad2,3 and collagen I were assayed by angiography and histomorphometric analysis. The protein of BMP-7,Smad2,3 were in the cell cytolymph.The number of staining cells were graded as follows:10-24%(+);25-49%(++);50-74%(+++);≥75%(++++).(2)Statistical analysisAll the datas were analysised with Wilcoxon analyses and the difference was significant (p<0.05)ResultThe protein of BMP-7,Smad2,3 were in the cell cytolymph. Following 8 weeks treatment,Telmisartan group displayed a significant reduction in Smad2,3 and collagen I(T=45,46.5, p<0.05 respectively). The BMP expression in Telmisartan and Telmisartan and eplerenon group were significantly higher than that in controls(T=16.5,18,p<0.05 respectively).Conclusion1. It was a significant reduction in the express of CollegonI in Telmisartan group.The result suggest that Telmisartan attenuates myocardical collagen synthesis in SHR.2. BMP-7 expression was significant higher in Telmisartan and Telmisartan and eplerenon group compared with control group. It was a significant reduction in the express of in The protein of Smad2,3 in Telmisartan group.The result suggest that BMP-7/Smads may play an important role in myocardial fibrosis.3. Telmisartan and eplerenon attenuates myocardical collagen synthesis in SHR possibly through down-regulating the expression of Smad2,3.