| Objective Many studies confirmed that renin-angiotensin-aldosterone system may play an important role in the process of hypertensive and myocardial fibrosis, angiotensin II (Ang II) is one of its main effector proteins, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker can prevent the formation or the effect of Ang II and attenuate myocardial fibrosis. In this study, to establish a myocardial fibrosis model of uninephrectomized rats by desoxycorticosterone acetate subcutaneous implanting, giving aliskiren intragastric administration in the mean time, observe the effects of desoxycorticosterone acetate and aliskiren on RAAS and myocardial fibrosis, and explore the effect of aliskiren on myocardial protection and its mechanism.Methods Forty five Male Sprague-Dawley rats were unilaterally nephrectomized. One week later, the rats were randomly divided into three groups as following:vehicle control rats(CON group)were implanted with Silicone rubber subcutaneously and limited drink tap water; desoxycorticosterone acetate-salt treated rats (DOC group): was implanted with Silicone rubber impregnated with DOCA (200 mg per rat) subcutaneously and had their drinking water replaced with 1% saline solution; aliskiren + desoxycorticosterone acetate treated rats(ALI group) implanted with Silicone rubber impregnated with DOCA (200 mg per rat)subcutaneously and limited drink 1% saline solution and intragastrically administrated with aliskiren in 50 mg/kg/d for 4 weeks. CON and DOC group were intragastrically administrated with equivalent physiological salt for 4 weeks. At the end of treatment, mean arterial blood pressure (MABP) were measured with catheterization. Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were analyed by Sirius red staining. Matrix metalloproteinase 9(MMP9), extracellular signal regulated kinase 1/2(ERK1/2), phosphorylated extracellular signal-regulated kinase 1/2(pERK1/2) were detected with Western blot analysis. RA and Ang II were detected with radiommoassay (RIA).Results Compared with CON group(15.87kPa±0.67kPa), MABP of DOC(23.73 kPa±1.50kPa)and ALI group(22.85 kPa±1.21kPa) were elevated significant(P<0.05) . But MABP of ALI group was not decreased significantly compared with DOC group (P>0.05).Myocardial fibrosis was observed in DOC group. Compared with the other two groups, the index of CVF and PVCA were increased significantly(P<0.05). Compared with CON group, the levels of MMP9, ERK1/2, pERK1/2 were inecreased significantly in DOC group (P<0.05), but the levels of RA and Ang II were decreased significantly in DOC group both in myocardial tissue and plasma (P<0.05). Compared with DOC group,the levels of MMP9, ERK1/2,PERK1/2,cardic RA and cardic Ang II were decreased significantly in ALI group (P<0.05),but RA and Ang II in plasma were not decreased significantly.Conclusion (1) Desoxycorticosterone acetate-salt treat can induce myocardial fibrosis in rats. (2) The renin inhibitor aliskiren can significantly attenuate the myocardial fibrosis induced by Desoxycorticosterone acetate-salt independent of the blood presure.. (3) DOCA-salt treat can inhibite plasma and myocardial tissue RAAS activity significantly, and activate signaling pathway of ERK1 / 2 and the expression of MMP9 in myocardial tissue. (4)The mechanisms of aliskiren attenuating myocardial fibrosis may be related to reduce generation of Ang II and MMP9 and inhibit the activation of ERK1/2 in lacal tissue. |
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