肺动脉高压大鼠肺组织肝细胞生长因子和c—met表达的变化  

Changes in expression of hepatocyte growth factor and c-met in lungs in a rat model of pulmonary hypertension

作　　者：林群[1] 雷立华[2] 曾邦雄[3] 林献忠[1] 林财珠[1] 郑辉哲[4] 杨庆[1] 蔡宏达[1] 高友光[1] 林健清[1] 

机构地区：[1]福建医科大学附属第一医院麻醉科,福州市350005 [2]福建省立医院麻醉科 [3]华中科技大学同济医学院附属协和医院麻醉科 [4]福建省肿瘤医院麻醉科

出　　处：《中华麻醉学杂志》2012年第3期284-287,共4页Chinese Journal of Anesthesiology

基　　金：基金项目：国家自然科学基金（30972972）;福建省自然科学基金（2011J01129）;福建省医学创新课题（2009-CXB-4）

摘　　要：目的观察肺动脉高压大鼠肺内肝细胞生长因子（HGF）及其受体（c—met）表达的变化。方法雄性SD大鼠80只，7周龄，体重180—250g，采用随机数字表法，将其随机分为2组（n=40）：对照组（c组）和肺动脉高压组（PH组）。PH组经左侧开胸行左肺切除术，手术结束后关胸，待自主呼吸恢复后拔除气管导管，2周后颈部皮下注射野百合碱60mg／kg，制备肺动脉高压模型；C组仅开胸，2周后颈部皮下注射等容量生理盐水。分别于注射野百合碱前1d（基础值）、注射野百合碱后7、14、21和28d时，各取8只大鼠，监测肺动脉压（mPAP），计算右心室与左心室＋室间隔质量比[RV／（LV＋s）]，计算肌型肺小动脉血管中膜相对厚度（RWT，和RWT2分别表示直径为50～100um和100—150um的血管中膜相对厚度）。采用RT-PCR法检测肺组织HGFmRNA和c-metmRNA的表达，采用Westem blot法检测肺组织HGF蛋白和c—met蛋白的表达，采用ELISA法检测肺组织转化生长因子-β（TGF-β）含量。结果与c组比较，PH组注射野百合碱后14、21和28d时mPAP、RV／（LV＋S）和RwL升高，HGF蛋白表达下调，注射野百合碱后7、14、21和28d时RWT1升高，肺组织HGFmRNA表达下调，TGF-β含量升高（P〈0．01），c-met mRNA及其蛋白表达差异无统计学意义（P〉0．05）。结论肺组织HGF合成不足可能参与了肺动脉高压的形成，其机制与肺组织TGF—β含量升高有关。Objective To investigate the changes in the expression of hepatocyte growth factor （HGF） and c-met in the lungs in a rat model of pulmonary hypertension. Methods Eighty 7 week old male SD rats weighing 180-250 g were randomly divided into 2 groups （ n = 40 each） ： control group （group C） and pulmonary hypertension group （group PH）. Pulmonary hypertension was induced by left pneumonectomy and subcutaneous monocrotaline （MCT） 60 mg/kg 2 weeks later. Pulmonary artery pressure and the ratio between the weight of right ventricle and left ventricle ＋ interventricular septum （RV/LV ＋ S） were measured at 7, 14, 21 and 28 d after MCT administration. HGF and c-met protein and mRNA expression and TGF-β content in the lung tissue were determined. Results Pulmonary hypertension and right ventricular hypertrophy associated with hypertrophy of pulmonary artery tunica media and muscularization of small pulmonary arteries developed after MCT administration in PH group. In PH group HGF protein and mRNA expression in the lungs was significantly down-regulated as compared with group C. There were no significant differences in c-met protein and mRNA expression in the lungs between the 2 groups. The TGF-β content in the lungs was significantly increased in group PH as compared with group C. Conclusion Decrease in HGF production in the lungs plays an important role in the pulmonary hypertension. Increasing of pulmonary TGF-β may play an important role in the down-regulation of pulmonary HGF expression during pulmonary hypertension.

关 键 词：肝细胞生长因子 原癌基因蛋白质c—met 高血压 肺性 

分 类 号：R543.2[医药卫生—心血管疾病]