Effect of chrysin on expression of NOX4 and NF-κB in right ventricle of monocrotaline-induced pulmonary arterial hypertension of rats / 药学学报

ABSTRACT

The aim of the present study is to investigate the protective effect of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension (PAH). PAH rats were induced by a single injection of monocrotaline (60 mg x kg(-1), sc) and were administered with chrysin (50 or 100 mg x kg(-1) x d(-1)) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expressions of collagen I, collagen III, NADPH oxidase 4 (NOX4) and nuclear factor-kappa B (NF-κB) were analyzed by immunohistochemisty, qPCR and (or) Western blot. The results showed that chrysin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by chrysin. The expressions of NOX4, NF-κB and MDA contents were obviously decreased, while the T-AOC was significantly increased in right ventricule from PAH rats with chrysin treatment. These results suggest that chrysin ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of NOX4 expression and antioxidant activity, and inhibiting NF-κB expression and collagen accumulation.