Effects of Icariin on Partial Vasoactive Substances in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model / 医药导报

ABSTRACT

Objective To investigate the effects of icariin (ICA) on partial vasoactive substances in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model.Methods Sixty male SD rats were randomly divided into five groupsnormal control group,model control group,ICA low-,middle-and high-dose (20,40,80 mg · kg-1 · d-1) group,12 rats in each group.Except for normal control group,the rats were injected with MCT (50 mg · kg-1 · d-1) to establish PAH model.After 1 week MCT-injection,ICA was given by intragastric administration for 3 weeks according to different groups.Mean pulmonary artery pressure (mPAP) was recorded through catheter connected with Power Lab system.Except for normal control group,the right ventricular hypertrophy index (RVHI) was calculated using formularight ventricle weight/the weight of left ventricle with septum× 100％.The morphology of lung artery was assessed by HE staining.Concentration of angiotensin Ⅱ (Ang Ⅱ),endothelin (ET),prostaglandine F2α(PGF2α),thromboxane A2(TXA2) and prostacyclin (PGI2) in serum was measured by ELISA kit assay.The protein levels of angiotensin converting enzyme (ACE),cyclooxygenase-2 (COX-2) and thromboxane A2 synthetase (TXAS) were analyzed by Western blotting,expression of ACE,COX-2 and TXAS mRNA was measured by real time RT-PCR.Results Compared with the normal control group,mPAP [(48.5±5.2) mmHg] and RVHI (33.3±3.8)％in model control group were significantly increased (P ＜ 0.05),the morphology revealed there was obvious artery remodeling at distal artery,the contents of Ang Ⅱ,PGFA2,TXA2 in serum were elevated,and ACE,COX-2 and TXAS gene expression was up-regulated in rats treated with MCT.ICA (40,80 mg · kg-1 · d-1) treatment significantly attenuated mPAP,RVHI and pulmonary artery remodeling (P ＜ 0.05),and decreased the contents of serum Ang Ⅱ,ET,PGF2β,TXA2,and PGI2,and inhibited the gene expression of ACE,COX-2 and TXAS.Conclusion ICA decreases the contents of AngⅡ,ET,PGI2,PGF2α and TXA2 in the serum of MCT-induced PAH rats,which may be one of the mechanisms underlying ICA inhibiting PAH.