目的探讨淫羊藿香( ICA)对野百合碱( MCT)诱导的的肺动脉高压( PA H )大鼠模型部分血管活性物质的 影响,以进一步明确ICA抗 PA H的作用机制.方法将 6 0 只 雄 性 S D大鼠随机分为正常对照组、模 型对照组和IC A小、中、大( 20,40,80 mg·kg-1·d-1) 剂量组,每组 1 2只.除正常对照组外,其他组大鼠皮下注射MCT(50 mg·kg-1·d-1) 复 制 PAH模型 ,1 周后按分组灌胃给药,连续 3 周.导管法测定平均肺动脉压( mPAP),分离右心室并称质量,计算右心室 肥厚指数( RVHI),苏木精-伊红( HE )染色观察肺小动脉病理改变并计算血管壁面积占血管截面积的百分比.酶联免疫 吸附测定( ELISA)法检测血清血管紧张素n (A n g n )、内皮素( ET)、前列腺素 F2 k(PGF2 k)、血 栓 素 ( TXA2) 和前列环素 (PGI2) 含量.Real time RT-PCR检测肺组织中血管紧张素转化酶( ACE)、环氧化酶 2 (COX -2 )和 TXA合 酶 ( TXAS) mRNA表达的变化.We伽m blotting检测肺组织中 ACE、 COX-2和 TXAS蛋 白 含 量 .结果与正常对照组相比,模型对 照组大鼠 mPAP[(48.5±5.2) mmHg]和 RVHI(33.3±3.8)%显著增高,肺 小 动脉管壁增厚,管 腔狭窄,重构明显.血清中 Angn、PGF2a和TXA2含量显著增高, ET和COX-2未见明显改变.ACE、 COX-2和 TXAS基 因 表 达 上 调 .经 IC A (2 0 ,4 0, 80·kg-1·d-1) 处理后, mPAP、RVHI和肺小动脉重构均有改善,其中 ICA(4 0,80 ·kg-1·d-1) 改善显著.IC A可 抑制 ACE、 COX-2和 TXAS基因表达,降低血清 A n g n、 ET、 PGF2 k、 TXA2 PGI2含量.结论 ICA可 降 低 PA H模型大鼠 血清中 Angn、 ET、PGI2、TXA2* PGF2a的含量,可能是 ICA抗 PA H的机制之一.
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 arteiy 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 for^nula : right ventricle weight/the weight of left ventricle with septumx100%.The morphology of lung artery was assessed by HE staining. Concentration of angiotensin n ( Ang n),endothelin (ET),prostaglandine F2 a(PGF2 a ) , thromboxane A2(TXA. )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 [ (4 8 .5 ± 5 .2 ) mmHg] and RVHI (3 3 .3 ± 3 .8 )%in model control group were significantly increased ( P 〈 0 .0 5 ) , the morphology revealed there was obvious artery remodeling at distal arter, the contents of Ang n , PGF2a ,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 AngniETGFiTXAgtand PGI2,a n d inhibited the gene expressio