氧化苦参碱预防与治疗野百合碱致肺动脉高压及对肺NO/PGI2/ET1失衡的调控作用

Oxymatrine is one of active alkaloid derived from Hui medicinal herb of Sophora alopecuroides L. It is well documented that oxymatrine has a variety of pharmacologic actions,including anti-myocardial and pulmonary ischemic injury, anti-inflammation and anti-tumor,etc. Our previous study showed that oxymatrine exerted pulmonary protective effects on monocrotaline-induced pulmonary hypertension，and its action mechanism is related to regulate of eNOS and ADMA pathway.Therefore, in the present study,to further elucidate the preventive and therapeutic effects of oxymatrine against pulmonary hypertension and obtain more experimental data for further application, the combined methods of pharmacology, molecular biology,histopathology and biochemistry are to be used; the dose-response preventive and therapeutic effects of oxymatrine on pulmonary hypertension in monocrotaline-induced pulmonary hypertensive rats will be observed,and the molecular mechanism of oxymatrine on abnormal NO/PGI2/ET1 pathway are to be investigated, including the effects of oxymatrine on regulation of eNOS/iNOS and L-arginine/arginase and PRMT/ADMA/DDAH metabolism pathway which affects NO production; modulation of RhoA/ROCK pathway and endothelin 1A and 1B receptor by endothelin-1; and regulation of COX1/COX2 and PGI2 systhases expression that governs PGI2 production.

氧化苦参碱是从宁夏特色回药材-豆科槐属植物苦豆子中提取的生物碱之一，具有抗心肌和肺组织缺血、抗炎和抗肿瘤等多种药理作用。我们前期研究结果显示：氧化苦参碱对野百合碱所致大鼠肺动脉高压具有预防作用，其机制与eNOS和ADMA信号通路有关。为此，本课题以大鼠肺动脉高压为模型，综合采用药理学、分子生物学、病理学和生物化学等方法与技术手段，进一步研究氧化苦参碱预防与治疗大鼠肺动脉高压的作用及其量效关系，并重点检测其对NO/PGI2/ET1通路失衡介导肺动脉高压的调控作用：包括影响NO生成的eNOS/iNOS和L-精氨酸/精氨酸酶水平，以及PRMT/ADMA/DDAH代谢途径；ET-1介导RhoA/ROCK通路的激活及其相应受体（ET-1A,1B）含量变化；影响PGI2生成COX1/COX2 和PGI2合成酶水平等。探讨氧化苦参碱预防与治疗肺动脉高压的作用与机制，为今后临床应用提供实验依据。