The Effect Of Oxymatrine On Myocardial COX-2/PGIS Expression In Rat With Chronic Heart Failure

ObjectiveThe present study was to investigate the protective effects of oxymatrine on regulation of the expression of cytosolic phospholipase A2(c PLA2), cyclooxygenase-1(COX-1), COX-2 and prostacyclin synthase(PGIS) in isoproterenol-induced rat heart failure.Methods1. The Sprague-Dawley rats, maintained on a normal diet, were randomly divided into five groups given control, oxymatrine(100 mg/kg)alone, ISO,ISO with oxymatrine(100 mg/kg)and ISO with oxymatrine(50 mg/kg),each group had 7 rats.2. Heart failure was induced in Sprague-Dawley rats by 5 mg/kg isoproterenol(ISO) subcutaneous injection for 7 days. In groups of ISO and ISO with oxymatrine(100 mg/kg or 50mg/kg), saline or oxymatrine was administered orally for 7 days prior to the ISO administration. Subsequently, ISO(5mg/kg) was administered subcutaneously for 7 days with saline or oxymatrine. In groups of control and oxymatrine(100 mg/kg) alone, saline was administered subcutaneously for 7 days.3. Serum brain natriuretic peptide(BNP) level, haemodynamic parameters, histopathological variables and expression of c PLA2, COX-1, COX-2 and PGIS in myocardial tissue were analysed.Results 1. After ISO 5mg/kg rat subcutaneous injection, maximal rate of decrease of left ventricular pressure(-LVd P/dtmin) was increased(P < 0.01), and Left ventricular systolic pressure(LVSP)was decreased(P < 0.01), and maximal rate of increase of left ventricular pressure(+LVd P/dtmax) was decreased(P<0.01), and the level of serum BNP was increased(P<0.01)than that of the control group. ISO aggravated the degree of cardiac interstitial fibrosis in rats. It presented that the ISO-induced heart failure model in rats is established.2. The heart failure rat was interfered by the OMT drugs, and after the intervention of the OMT the-LVdp/dtmin was decreased significantly(ISO+OMT100mg/kg P<0.05,ISO+OMT50mg/kg P<0.01),and the +LVdp/dtmax are significantly increased(ISO +OMT100mg/kg P<0.05), and the LVSP was increased significantly(ISO+OMT100mg/kg,ISO+OMT50mg/kg,P<0.05), and the level of serum BNP was decreased(ISO+OMT100mg/kg, ISO + OMT50mg/kg, P < 0.01). Histopathological examination demonstrated that oxymatrine could inhibit cardiac interstitial fibrosis in the ISO-induced heart failure rats. There was no difference between the control group and the OMT100mg/kg group in the haemodynamic parameters and the serum BNP level.3. Oxymatrine exerted no effects on ISO-induced elevated protein c PLA2 expression.(P>0.05),oxymatrine inhibited COX-1 expression(P<0.01), and increased myocardial expression of COX-2(P<0.01)and PGIS(P<0.01)in ISO-induced heart failure rat. The expression of these proteins had no difference between the two doses application of the OMT, and between the control group and the OMT100mg/kg group.ConclusionsOur results suggest that the favourable effects of oxymatrine for management of heart failure are probably achieved by regulation of the COX-1, COX-2 and PGIS expression.