Ang-1／Tie2在大鼠体-肺分流肺动脉高压形成中的作用.docVIP

Ａｎｇ-１／Ｔｉｅ２在大鼠体－肺分流肺动脉高压形成中的作用 　　作者：王伟,梁孟亚,张希,王治平　　作者单位：中山大学附属第一医院心脏外科， 广东 广州 　　【摘要】 目的】 探讨Ang-1及其受体Tie2在体-肺分流肺动脉高压形成过程中的作用。【方法】 分流组20只大鼠行左颈总动脉-左颈外静脉分流手术，对照组16只大鼠行假手术。分别于术后4周和8周测量右心室收缩压，并对大鼠肺组织进行组织学分析，测量肺微细动脉壁厚度指数。通过实时荧光定量RT-PCR和Western Blot的方法，检测大鼠肺组织中Ang-1和Tie2的表达。同时，通过Western Blot检测caspase-3及激活型caspase-3的表达。【结果】 与对照组相比，分流组大鼠术后第4周和第8周右心室收缩压明显升高。组织学分析发现，分流组大鼠肺微细动脉内膜内皮细胞增生肥大，血管壁厚度指数增加。在分流引起肺动脉高压形成的过程中，Ang-1和Tie2在mRNA及蛋白水平上均明显增加。与此同时，标志细胞调亡的激活型caspase-3的表达却明显下降。 【结论】 Ang-1和Tie2的表达与肺动脉高压紧密相关。Ang-1/Tie2系统可能通过抑制内皮细胞凋亡，促进体-肺分流肺动脉高压的形成。 　　【关键词】 血管生成素-1; Tie2; 肺动脉高压; 凋亡; caspase-3; 大鼠 　　Roles of Angiopoietin-1/Tie2 in Development of Shunt-inducedRat Pulmonary Arterial Hypertension　WANG Wei， LIANG Meng-ya， ZHANG Xi， WANG Zhi-ping*　Department of Cardiac Surgery， the First Affiliated Hospital， SUN Yat-sen University， Guangzhou 510080， China　Abstract：【Objective】 To elucidate possible roles of angiopoietin-1 and its receptor Tie2 in the development of shunt-induced pulmonary arterial hypertension. 【Methods】 Twenty Spargue-Dawley rats in shunt groups underwent left common carotid artery-external jugular vein shunt operation， and 16 rats in control groups received sham operation. At week 4 and 8 of the study， right ventricular systolic pressures were measured. Histologic analysis of lung tissue was performed and the percentages of vascular wall thickness of pulmonary arterioles were also measured. The expression of Ang-1 and Tie2 was investigated by real-time reverse transcriptasendash;polymerase chain reaction (RT-PCR) and Western Blot in the lung. The expression of caspase-3 and cleaved caspase-3 was also investigated by Western Blot. 【Results】 Compared with control groups， shunt induced significant increase in right ventricular systolic pressures at week 4 and 8. Histologic analysis of the lungs in shunt groups exhibited endothelial cell hypertrophy and proliferation in the intima of pulmonary arterioles along with increase of percentages of vascular wall thickne