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Objective:To investigate the effects of Osthole(Ost) on the right ventricle remodeling in monocrotaline-treated rats,and to explore the mechanisms.Methods:200~220 g male Sprague-Dawley rats were randomly divided into normal control group(Control,n=8),model group (Model,n=8),low dose of Ost treatment group(Ost-L,10 mg·kg-1,n=8),high dose of Ost treatment group(Ost-H,20 mg·kg-1,n=8) and sildenafil treatment group(Sildenafil,25 mg·kg-1,n=8).All rats were given a single dose of MCT 50 mg·kg-1 subcutaneously to establish the right ventricle remodeling except normal control group. Then the rats in the Ost and sildenafi l treatment group were gavaged once daily from 1 day to 28 days. The other rats in the model group and normal control group were given the same amount of ddH2O with 0.5% be tween 80. After 28 days of administration,the right ventricular pressure were measured by right heart catheterization. Right ventricle(RV) and left ventricle plus septum (LV+SEP) were weighed separately. RV hypertrophy index(RVHI) were measured by the relative weight ratio of RV to LV+SEP. The morphological change of the RV were executed by light microscope and transmission electron microscope.The cardiomyocytes apoptosis were detected by TdT mediated nick dUTP end-labeling(TUNEL) method using the paraffi n-embedded right ventricular tissues. The mRNA expression of Bcl-2,Bok and p53 were examined by real time RT-PCR. The protein expression of Bcl-2,Bax,Bok,IκB,IL-6,TNF-α and the levels of Cleaved caspase 3,p-NF-κB(p65) were detected by western blotting.Results:Compared with the control group,the right ventricular pressure and RVHI were increased obviously(P<0.05),myocardial hypertrophy,structure disorders,mitochondrial swelling and cardiomyocytes apoptosis(P<0.05) were observed in model group. The mRNA expression of Bok and p53 in right ventricular tissues were up-regulated(P<0.05),and the mRNA expression of Bcl-2 was down-regulated in model group(P<0.05).The protein expression of Bax,Bok,IL-6,TNF-α and the levels of Cleaved caspase 3,p-NF-κB(p65) were up-regulated(P<0.05),and the protein expression of Bcl-2 and IκB were down-regulated signifi cantly in model group(P<0.05). Compared with the model group,the right ventricular pressure and RVHI were decreased(P<0.05),myocardial hypertrophy, structure disorders,mitochondrial swelling and cardiomyocytes apoptosis(P<0.05) were improved signifi cantly in Ost and sildenafi l treatment group. The mRNA expression of Bok and p53 were down-regulated(P<0.05),while the mRNA expression of Bcl-2 was up-regulated(P<0.05) in Ost and sildenafi l treatment group. The protein expression of Bax,Bok,IL-6,TNF-α,and the levels of Cleaved caspase 3,p-NF-κB(p65) were down-regulated(P<0.05),and the protein expression of Bcl-2 and IκB were up-regulated signifi cantly in Ost and sildenafi l treatment group(P<0.05).Conclusions:Ost can resist the RV remodeling induced by MCT in rats,which may be related to these possible mechanisms:① Ost inhibits cardiomyocytes apoptosis by regulating Bax/Bcl-2 pathways;② Ost attenuates infl ammation by inhibiting NF-κB pathway.