急性缺氧性肺动脉高压兔心肌细胞凋亡和相关基因的表达

Changes of apoptosis and expression of apoptosis genes in the myocardium of rabbits with actue hypoxia-induced pulmonary hypertension

目的探讨急性缺氧性肺动脉高压(PAH)兔模型心肌组织的细胞凋亡,以及基因bcl-2、Bax、Fas、FasL和Caspase-3在左室心肌细胞中的表达。方法采用呼吸机建立急性缺氧肺动脉高压兔模型,分为对照组(n=10)和缺氧PAH组(n=20),采用TUNEL标记法检测兔模型心肌组织中的凋亡细胞,并运用免疫组化及原位分子杂交技术研究基因bcl-2、Bax、Fas、FasL和Caspase-3在左室心肌细胞中的表达。结果缺氧PAH组左室心肌细胞凋亡指数为(17±3),明显高于对照组(2±0.3);缺氧PAH组左室心肌Bax、Fas、FasL和Caspase-3蛋白和mRNA表达显著上调,与对照组相比均有显著性差异(P<0.01),缺氧PAH组左室心肌bcl-2蛋白和mRNA表达呈弱阳性。结论细胞凋亡参与了急性缺氧肺动脉高压的发生及发展,急性缺氧性PAH发生后,促凋亡基因和抑制凋亡基因的表达在左心室的平衡被打破。

Objective To explore apoptosis and the expression of bcl-2, Bax, Fas, FasL and Caspase-3 genes in the myocardium of rabbit models with hypoxia-induced pulmonary artery hypertension（PAH）. Methotis The rabbit models of hypoxia pulmonary hypertension were made with ventilators, Thirty rabbits were divided into the control group and the hypoxia-induced PAH group randomly. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL）were used to detect the changes of apoptosis. Protein and mRNA expression of bcl-2, Bax, Fas, FasL and Caspase-3 genes were evaluated by SP immunohistochemical staining and in situhybridization assays in the left ventricular myocardial tissues, Results The index of cardiomyocyte apoptosis in hypoxia-induced PAH group increased significantly in comparison with that in control group（P〈0.01）. The mRNA and protein expression of Bax, Fas, FasL and Caspase-3 genes in the left ventricular myocardium of rabbits with hypoxia-induced PAH group were significantly higher than that in normal controls（ P 〈 0.01 ）. Conclusions Myocardial apoptosis was involved in the acute hypoxia-induced pulmonary artery hypertension（PAH）. The balance between the expression of apoptosis genes and sitimulating apoptosis genes in left ventricular myocardium in acute hypoxia-induced pulmonary artery hypertension is broken.