内源性一氧化氮合酶抑制物在肺心病肺动脉高压中的作用机制研究  

Research about the mechanism of endogenous inhibitor of nitric oxide synthase in Pneumocar dial disease and pulmonary hypertension

作　　者：曹仕鹏[1] 诸兰艳[1] 

机构地区：[1]长沙市中心医院胸科中心6病室,湖南长沙410000

出　　处：《临床医药实践》2010年第6X期676-679,共4页Proceeding of Clinical Medicine

基　　金：国家"十一五"科技重大专项课题(课题编号:20092×1005-018)

摘　　要：目的:了解内源性一氧化氮合酶抑制物(ADMA)对肺动脉内皮舒张功能、肺血管重构及右心功能的影响,探讨其与肺心病肺动脉高压的关系。方法:临床部分:肺心病合并肺动脉高压患者62例,对照组48例。用高效液相色谱法检测血浆ADMA浓度,用硝酸还原酶法测定血浆中NO的浓度。动物实验:动物分为对照组、模型组及治疗组,每组10只。采用皮下注射野百合碱建立肺动脉高压模型。治疗组造模第2天开始给L-精氨酸100 mg/kg每日腹腔注射。每周监测尾动脉压,4 w后颈外静脉插管检测肺动脉压力及右心室功能,并检测肺动脉舒张功能。检测血浆ADMA,NO浓度;肺组织DDAH2mRNA及肺动脉DDAH2蛋白的表达。结果:肺心病患者血浆ADMA浓度显著高于正常对照组(P<0.05),血浆NO水平显著低于正常对照组(P<0.05)。与对照组比较,肺动脉高压组大鼠肺动脉压力值增高(P<0.05);右心室肥厚明显(P<0.05);右心功能减弱;肺动脉舒张功能降低;肺小动脉显著增厚。L-精氨酸治疗后大鼠肺动脉压力降低(P<0.05),右室肥厚减轻(P<0.05),右心功能得到一定程度改善;肺动脉舒张功能得到一定程度恢复。肺动脉高压组大鼠肺组织中DDAH2mRNA表达显著下调;肺动脉内皮DDAH2蛋白表达下调。与对照组比较,肺动脉高压组大鼠血浆ADMA浓度明显升高(P<0.05),血浆NO含量显著降低。L-精氨酸治疗后血浆ADMA浓度降低(P<0.05);血浆NO水平升高(v<0.05)。血浆ADMA浓度与肺动脉压力呈正相关(r=0.805);与右心室肥厚指数亦呈正相关(r=0.668)。结论:ADMA可能通过影响肺动脉内皮舒张功能及调节血管重构而参与肺动脉高压的病理过程。ADMA可能参与诱导右心肥厚、右心功能衰竭而促进肺心病的发展。Objective:This experiment is to study the role of ADMA on Endothelial Function,pulmonary vascular remodeling,right ventricular function and the relationship of ADMA and pulmonary heart disease and pulmonary hypertension.Methods:The Clinical Part:Select newly diagnosed and untreated PHD patients also with pulmonary hypertension,the number is 62.48 cases in control group.Collect the elbow vein blood and the plasma was separated for the detection of ADMA and NO.Animal Part: Male SD rats were divided into treatment group and control group,the model of group,each group 10.Treatment group and the model of groups rats were received a single hypodermic injection of monocrotaline for the foundation of PH model.L-arginine treatment group received a intraperitoneal injection of L-arginine from the 2nd day after monocrotaline injection.Four weeks after MCT injection,after the detection of pulmonary arterial pressure and right ventricular function,the blood was obtained from common carotid artery,then heart and lung were brought out rapidly.Plasma concentration of ADMA and NO was measured.Detection of lung tissue DDAH2mRNA and pulmonary DDAH2 protein expression.Results:The plasma concentration of ADMA in patients with PHD was significantly higher than the normal control group(P<0.05),while the plasma NO level was significantly reduced(P<0.05).In monocrotaline-induced PH rats,pulmonary arterial pressure increased significantly(P<0.05).There was an obvious right ventricular hypertrophy(P<0.05),right heart failure,reduced diastolic function in pulmonary artery and significant pulmonary artery thickening.The plasma concentration of ADMA was significantly increased(P<0.05) which is closely related to pulmonary arterial pressure(r=0.805) and right ventricular hypertrophy(r=0.668).Congclusion:ADMA may affect the pulmonary artery endothelial function and regulation of vascular remodeling which is involved in the pathological process of PH.ADMA may be involved in induction of right ventricular hypertrophy,right heart failure and to pr

关 键 词：肺心病 肺动脉高压 右心衰竭 非对称二甲基精氨酸 二甲基精氨酸二甲胺水解酶 

分 类 号：R541.5[医药卫生—心血管疾病]