Protective Effects Of Matrine On Isoproterenol-induced Chronic Heart Failure Via Regulation Of ENOS And RhoA/ROCK1 Signaling Pathways In Rats

Objectives To investigate the protective effect of matrine on rats withisoproterenol(ISO)-induced chronic heart failure via the regulation of e NOS anRho A/ROCK1 signaling pathways in the cardiomyocytes.Methods Chronic heart failure was induced in rats by subcutaneous injection of ISO(5 mg·kg-1) for seven consecutive days. Male Sprague-Dawley rats were randomly divided into the normal control groups, the isoproterenol(ISO) group(chronic heart failure model), the matrine treatment group(50, 100 and 200 mg·kg-1), the single-use matrine group(200 mg·kg-1), and Propranolol group(10 mg·kg-1). Rats were pretreated with matrine(50, 100 and 200 mg·kg-1) orally 1 h before the subcutaneous injection for seven consecutive days. Hemodynamic(Heart rate, blood pressure, LVSP,LVd P/dtmax,LVEDP and LVd P/dtmin) and biochemical parameters were measured. The inhibition of histopathological injuries in the rat myocardial tissues was observed under the exposure to different doses of matrine.The serum levels of NO and ADMA were determined by enzyme-linked immunosorbent assays and biochemical methods. The expressions of e NOS, p-e NOS(Ser1177), Rho A and ROCK1 were analysed by western-blot.Results Oral administration of matrine(100 and 200 mg·kg-1 for 7days) significantly improved the dysfunction of left ventricular(LV) including increased left ventricular systolic pressure(LVSP), maximal rate of increase of left ventricular pressure(LVd P/dtmax), maximal rate of decrease of left ventricular pressure(LVd P/dtmin), left ventricular end-diastolic pressure, heart rate and systolic blood pressure. The histopathological study showed that matrine attenuated myocardial necrosis, infiltration of inflammatory cells, interstitial edema and other abnormalities in rats with ISO-induced chronic heart failure. Compared with the control group, ISO-treated rats showed that the serum NO level was reduced and that the serum ADMA level was elevated. Meanwhile, the expressions of e NOS and p-e NOS(Ser1177) were reduced and those of Rho A and ROCK1 were increased in rats with ISO-induced chronic heart failure. Matrine(50, 100 and 200 mg·kg-1)significantly increased NO and reduced ADMA in the serum. Matrine(100 and 200 mg·kg-1) increased the expression of e NOS and p-e NOS(Ser1177) in the cardiomyocytes, and simultaneously reduced that of Rho A and ROCK1. Matrine(50 mg·kg-1)did not significantly affect the expression of p-e NOS(Ser1177), e NOS and Rho A. Matrine( 200 mg·kg-1) alone neither influnced myocardial tissues nor the expression of the above-mentioned proteins.Conclusions Our results show that matrine may protects against isoproterenol-induced myocardial ischemia in rats via the regulation of e NOS and Rho A/ROCK1 signaling pathways.