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 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.
ABSTRACT
Aim To investigate the effect of Isorhynchophylline(Isorhy)on platelet aggregation or thrombosis,and explore the mechanism of it's action.Methods Rat platelet aggregation was determined.cAMP contents were assessed by Born's method and radioimmunoassay respectively.The effect of Isorhy on rat's thrombosis was observed with the thrombogenesis model of artery-vein bypass.Results Isorhy(0.65 mmol?L-1,1.30 mmol?L-1)was shown to markedly inhibit the rat's platelet aggregation induced by ADP or thrombin in a concentration-dependent manner(P
ABSTRACT
AIM To study the distrubution and excretion of protopine in rats. METHODS Reversed phase high performance liquid chromatographic method (RP HPLC) was developed for determining the level of protopine in rats. The analytical column were packed with 5 ?m C 18 . The mobile phase was a mixture of methanol, water and 10% acetic acid (80∶20∶2), in which the pH was modulated to 5 6 with 15% ammonia. Protopine biological samples were isolated well, in which two extraction with ether under basical condition and an extraction with 0 02 mol?L -1 sulfuric acid were performed, respectively. The content of protopine in the biological sample was measured by an UV detector at 285 nm. The distrubution and excetion of protopine have been investigated in rats after intravenous administration 10 mg?kg -1 . RESULTS Protopine distrubuted in many tissues after iv a dose of 10 mg?kg -1 . The higher level of protopine was found in lung, kidney, spleen and brain, and the highest was observed in lung at 5, 15 minutes after administration. However the top level tissue was testicle at 3 h, which may be due to small blood circulation. The excretion of the parent compound in urine was 36 87% of dose, but the excretion of the parent compound in feces and bile was less than 1% of dose. Plasma protein binding was less than 5%. CONCLUSION The distrubution of protopine is extensive and the parent compoud was mainly excreted by urine and plasma protein binding was low.
ABSTRACT
The effects of Rhynchophylline (Rhy) and Isorhychophyiline (Isorhy), the alkaloids abstracted from the Chinese traditional herb Uncaria rhynchophyllia (Miq) Jackson, on the 45Ca-influx and efflux were investigated in rabbit aorta. Both Rhy and Isorhy (10 ?mol? L-1) inhibited the 45Ca-influx induced by high K+(77. 0 mmol ? L-1), but neither significant-ly influenced the 45Ca-influx and efflux induced by noradrenaline (10 ?mol ? L-1). The results suggest that these alkaloids block the Voltage-dependent calcium channel.