吸入一氧化氮对左向右分流型先心病合并重度肺动脉高压的肺血管平滑肌细胞凋亡调控的影响  

Study on Vascular Smooth Muscle Cell Apoptosis in Lungs Induced by Nitric Oxide in Congenital Heart Disease and Pulmonary Hypertension

作　　者：赵康丽[1] 刘迎龙[1] 于存涛[1] 谢宁[1] 宋晓东[2] 

机构地区：[1]中国医学科学院阜外心血管病医院,北京市100037 [2]中国医学科学院阜外心血管病医院中德分子医学中心

出　　处：《中国分子心脏病学杂志》2005年第5期725-728,F0003,共5页Molecular Cardiology of China

摘　　要：目的研究拟用形态学方法TUNEL染色观察肺动脉增生组的肺小动脉平滑肌细胞的凋亡情况和分子生物学的方法DNALadder及PCR反转录反应研究肺血管平滑肌细胞凋亡基因Bcl-2和基因Bax表达,以探讨NO是否可以通过调控凋亡相关基因表达来调控肺血管平滑肌细胞凋亡这一途径,实现对先心病肺动脉高压的治疗以及开发术前治疗肺动脉高压新方法具有重要意义。方法于2001年3月—7月共选择先心病患儿15例,分为4组。男10例,女5例,年龄小于5岁,0.5～5(2.9±1.5)岁。组1为肺动脉平滑肌增生吸入NO治疗组共6例,包括室间隔缺损2例和完全心内膜垫4例均合并重度肺动脉高压每日吸入5～10ppmNO2—4h,约10～14d;组2为肺动脉平滑肌增生对照组,不吸入NO治疗共3例,包括室间隔缺损2例和完全心内膜垫1例均合并重度肺动脉高压;组3为正常肺动脉对照组共3例,包括3例房间隔缺损合并轻度肺动脉瓣狭窄;组4为肺动脉发育不良对照组共3例,均为法鲁氏四联症。于术中,体外循环后取右肺中叶肺组织1×1cm3分别行TUNEL染色和DNALadder及PCR实验测定Bcl-2基因和Bax基因表达。结果形态学TUNEL染色方法显示左向右分流型先心病合并重度肺动脉高压,吸入NO治疗组与正常肺动脉组比较,肺小动脉平滑肌细胞凋亡增多;而未吸入NO对照组与正常肺动脉组比较则反之,肺小动脉平滑肌细胞凋亡细胞极少。ASD+轻度PS、TOF和VSD+PH吸入NO治疗的基因Bax表达上调。左向右分流型先心病合并重度肺动脉高压未吸入NO对照组的肺血管平滑肌细胞凋亡基因Bcl-2表达上调,Bax基因表达下调;吸入NO治疗组的肺血管平滑肌细胞凋亡基因Bax表达上调,Bcl-2表达下调。结论比两组肺动脉增生组的患者,NO对肺动脉高压的治疗主要是通过对细胞凋亡基因表达的调控而达到治疗目的。Objective Study on treatment of pulmonary hypertension in congenital heart disease by NO from the view of cell apoptosis and gene expression will explain the pathophysiology of pulmonary hypertension in a new level and is of significance in research of genesis, development and treatment of pulmonary hypertension. This study is to use methods of molecular biology such as DNA Ladder and RT-PCR to detect expression of cell apoptosis gene Bcl-2 and Bax and find out whether NO can regulate smooth muscle cell apoptosis through regulation of apoptosis related gene expression. Methods 15 patients of congenital heart disease were selected from 2001.3 to 2001.7. there were 10 male patients and 5 female patients, with age ranged from 0.5 to 5 years old（mean 2.9 ± 1.5 years old）. Patients were divided into 4 groups. Group 1 included 2 cases of ventricular septal defect and 4 cases of total atrioventrieular canal defect with severe pulmonary hypertension. Patients in group 1 were treated with inhalation of 5 - 10 ppm NO and pure oxygen 2 - 4 hours a day for 10 to 14 days. Heart rate, blood pressure and oxygen saturation are monitored. Group 2 included 2 cases of ventricular seotal defect and 1 case of atrioventricular canal defect with severe pulmonary hypertension without inhalation of NO before operation. Group 3 included 3 cases of atrial septal defect without pulmonary hypertension. Group 4 included 3 cases of Tetrology of Fallot. Results Showed increase of expression of the vascular smooth muscle cell apoptosis gene Bax and decrease of Bcl-2. This indicated that treatment effect of NO to pulmonary hypertension is mainly via the regulation of cell apoptosis gene expression. Conclusions We speculated that NO can increase cell apoptosis and inhibits endothelial cell and smooth muscle cell over proliferation, thus inhibits pulmonary vascular remodeling.

关 键 词：左向右分流 先心病 重度肺动脉高压 NO 基因调控 

分 类 号：R541.1[医药卫生—心血管疾病]