血管紧张素Ⅱ对动力性肺动脉高压左室心肌细胞凋亡及纤维化的影响

Effect of Angiotensin II in Apoptosis and Myocardial Interstitial Fibrosis of the Left Ventricular Myocardium with Dynamical Pulmonary Hypertension

目的观察先天性心脏病(congenital heart disease,CHD)合并肺动脉高压(PAH)患儿心肌细胞凋亡、心肌纤维化及与血浆血管紧张素Ⅱ含量的关系。方法根据有无合并肺动脉高压将20例CHD患儿分为2组,CHD组(n=8)和CHD合并PAH组(n=12),对照组(n=5)为单纯缺血缺氧性脑病患儿。采用TUNEL标记法检测心肌组织中的凋亡细胞,用免疫组化法检测左室心肌细胞I型和Ⅲ型胶原蛋白的表达,采用放射免疫法测定血浆血管紧张素Ⅱ浓度。结果CHD组和CHD合并PAH组心肌细胞凋亡指数明显高于对照组,两组左室心肌组织I型和Ⅲ型胶原蛋白呈强阳性表达,与对照组相比差异有统计学意义;CHD及CHD合并PAH组血浆AngⅡ水平均显著高于对照组,CHD合并PAH组高于CHD组,且两组相比较有统计学意义。血浆AngⅡ与心肌细胞凋亡指数和Ⅲ型胶原蛋白表达量呈正相关关系,而肺动脉压与心肌细胞凋亡指数和Ⅲ型胶原蛋白表达量及I型胶原蛋白表达量无相关关系。结论在CHD患儿左室心肌细胞凋亡和纤维化的过程中,AngⅡ可能比肺动脉压力发挥着更重要的作用,所以应用ACEI阻断肾素-血管紧张素加以降低肺动脉压对提高降低病死率有重要意义。

Objective To investigate the relationship between apoptosis, myocardial interstitial fibrosis of left ventficular myocardium of babies with congenital heart disease（CHD） and with pulmonary artery hypertension（PAH） and the concentration of angotensin Ⅱ of plasma. Methods 5 unexpected death neonates were studied as the control group, 10 babies with congenital heart disease（CHD） with pulmonary artery hypertension（PAH）, and 8 with congenital heart disease（CHD） without PAH were studied as the experimental group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL） were used to detect the changes of apoptosis. Expressions of Ⅰ and Ⅲ type collagen protein were evaluated by SP immunohistochemical staining. The concentration of angiotensinⅡ in plasma was detected by radioimmunoassay. Results The index of cardiomyocyte apoptosis in CHD with PAH group and single CHD group increased significantly in comparison with that in control group（P 〈0.01）. Compared with the control group, the expression of Ⅰ and Ⅲ type collgen protein in the left ventficular myocardium significantly increased, it was significant in statistics（ P 〈0.01）. The plasma angiotensin Ⅱ in CHD with PAH or single CHD group was significantly higher than that of the control group （P 〈 0. 01）. Compared with that of the single CHD group, the concentration ofangiotensin Ⅱ of plasma in the CHD with PAH group elevated , there was statistic significance （ P 〈 0. 0 5 ） .Plasma concentration of angiotensin Ⅱ of CHD with PAH was positively correlated with the index of eardiomyocyte apoptosis and expression of Ⅲ type collagen protein, but pulmonary artery systolic pressure is not significantly correlated with the index of cardiomyocyte apoptosis and expression of Ⅲ type collgen protein. Conclusion In the course of apoptosis and interstitial fibrosis in the left myocardium of CHD with PAH, the angotensin ,Ⅱ may play a more important role than pulmonary artery pressure. ACEI can block rein-angotensin, it has important effect on reducing fatality rate in babies of CHD with PAH.