RESUMO
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 groups:normal 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 formula:right 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.
RESUMO
[ ABSTRACT] AIM:To investigate the inhibitory effect of ginsenoside Re on intimal hyperplasia induced by bal-loon-injury and to explore the role of NF-κB p65 signaling pathway in the process.METHODS:SD rats (n=40) were di-vided into 5 groups randomly: sham operation group, model group, low-dose ginsenoside Re group, middle-dose ginsen-oside Re group and high-dose ginsenoside Re group.The carotid artery intima injury model was established by 2F balloon catheters in all groups except the sham operation group.The day after modeling, the animals in model group and sham op-eration group were administered intragastrically with distilled water, and the rats in low-dose, middle-dose and high-dose ginsenoside Re groups were given ginsenoside Re at doses of 12.5 mg/kg, 25mg/kg and 50 mg/kg, respectively.After 14 continuous days, the morphological changes of the injured arteries were observed by HE staining and the lumen area, intima area and media area as well as the ratio of intimal area/media area were determined.The expression of tumor necrosis fac-tor-α( TNF-α) and interleukin-1β( IL-1β) were detected by real-time PCR.The proliferating cell nuclear antigen ( PC-NA) and nuclear factor-kappa B ( NF-κB) p65 were examined by immunohistochemistry.RESULTS:Compared with sham operation group, the vessel cavity was narrowed (P sion of PCNA and NF-κB p65 were decreased in medium and high-dose ginsenoside Re groups (P<0.05).CONCLU-SION:Ginsenoside Re inhibits the vascular neointimal hyperplasia induced by balloon-injury in rats, and the molecular mechanism may be related to the inhibition of NF-κB p65 signaling pathway.