Protective Effects Of Rhynchophylline On Cardiac Activity In Spontaneously Hypertensive Rats And Its Relative Mechanism Research

Objective: The purpose of this research is to observe the protective effect of Rhy on left ventricular remodeling in SHR and explore its possible mechanism.Methods : 32 male SHR were choosed and averagely divided into rhynchophylline high and low dose group(20, 5mg·kg-1·d-1, n=8), SHR model group(distilled water 5ml·kg-1·d-1, n=8), captopril positive control group(17.5 mg·kg-1·d-1, n=8) at random. In addition, the WKY were choosed as blank control group(distilled water 5ml·kg-1·d-1, n=8). All groups were treated daily with these corresponding dosages for 10 weeks. Blood pressure was measured by tail cuff every 2 weeks before and during administration. After 10 weeks, the wet weight of whole heart and left ventricular were measured, and the heart viscera indices were calculated. Moreover, basic myocardial histopathological changes and myocardial collagen fibres changes were observed by HE staining and Masson staining respectively. Besides, numerous assays were appied to detect the content of relevant biochemic indices(HYP, AngⅡ, MDA), enzymes(SOD, i NOS), signaling protein(TGF-β1, Smad3, Smad7, MMP-9, TIMP-l), and cytokines(TNF-α, CTGF).Results:(1) Compared with the normal group, SBP and DBP of model group was significantly increased(P<0.01); compared with the model group, SBP and DBP of groups treated with high and low dose of rhynchophylline significantly decreased at the beginning(P<0.01). Moreover, this decline effect reached steady state after 8 weeks. Therefore, compared with the captopril group, there is evident shows that the antihypertensiveeffect of each dose group administrated with rhynchophylline could lastingly lower blood pressure(P<0.01 or P<0.05).(2) Compared with the normal group, cardiac index of model group significantly increased(P<0.01 or P<0.05). At the same time, the cardiac weight index of group treated with rhynchophylline obviously decreased in dose-dependent manner(P<0.01).(3) Contrasted with normal cardiac tissue, model group presented that the hypertrophied and disorganized myocardial cell, enlarged and stained nucleus, widened myocardial cell gap, infiltration of inflammatory cells, a clear blue stain exsiting in interstitial myocardial and vascular, numerous and disorganized myocardial interstitial and perivascular fibrous tissue with severe collagen deposition by using HE staining and Masson staining. All these phenomenons were remarkably alleviated by treating rats with rhynchophylline or captoril.(4) Compared with the normal group, the levels of AngⅡ was significantly increased in plasma and myocardium(P<0.01) in model group. Meanwhile, in plasma and myocardium, compared with the model group, the content of AngⅡ was significantly decreased(P<0.01) in the group fed with rhynchophylline at high and low dose and captopril. Besides, rhynchophylline group presented more effective action than the group treated with captopril(P<0.01).(5) Compared with the normal group, the levels of HYP, MDA and TNF-α were significantly increased and SOD were obviously decreased in serum of SHR(P<0.01). Compared with the model group, the levels of myocardial HYP, MDA and TNF-α in serum were significantly decreased and SOD were obviously increased in sequoyitol group or acarbose group(P<0.01 or P<0.05).(6) Compared with the normal group, model group showed high expression of TGF-β1, Smad3, i NOS, CTGF, MMP-9, TIMP-1 and the ratios of MMP-9, TIMP-1 in myocardial tissue(P<0.01). Nevertheless, the expression of Smad7 was appeared with lower content(P<0.01). Compared with the model group, rhynchophylline or captorilobviously down-regulated the expression of TGF-β1, Smad3, i NOS, CTGF, MMP-9, TIMP-1 in myocardial tissue and the ratios of MMP-9, TIMP-1(P<0.01 or P<0.05). In addition, rhynchophylline or captoril could remarkably up-regulated the expression of Smad7(P<0.01 or P<0.05).Conclusions:(1) Rhynchophylline can significantly reduce blood pressure of SHR and the organ coefficient.(2) Rhynchophylline remarkably ameliorated myocardial remodeling and collagen deposition in SHR.(3) Rhynchophylline can evidently decrease the levels of HYP and TNF-α in SHR.(4) Rhynchophylline significantly decreased the level of myocardial MDA and obviously increased the content of SOD in SHR.(5) Rhynchophylline obviously down-regulate the expression of TGF-β1、Smad3、i NOS、CTGF、 MMP-9、TIMP-1 and the ratios of MMP-9, TIMP-1, simutaneously up-regulate the expression of Smad7 protein in myocardial tissue of SHR.