凋亡机制在先天性心脏病肺动脉高压肺血管结构改建中的作用

Role of apoptosis versus proliferation in pulmonary artery remodeling pulmonary hypertension secondary to congenital disease

目的 研究凋亡机制在左向右分流性先天性心脏病 (CHD)肺动脉高压的致病过程中的作用和凋亡因素的作用机制。方法 应用免疫组化及原位缺口末端DNA标记技术 ,检测肺动脉血管壁细胞的增殖、凋亡情况。用免疫组化检测凋亡相关bcl 2和bax的表达。结果 CHD病人肺动脉的结构发生明显改建 ,CHD及对照组肺内都有增殖与凋亡的细胞 ,但CHD组增殖细胞多而凋亡细胞明显减少。bcl 2在CHD组中表达强度明显高于对照组 ,而bax在对照组中的表达高于CHD组。结论 在肺血流量增加、血流冲击、缺氧等因素作用下 ,bcl 2和bax两种基因表达比例发生变化 ,使肺动脉壁细胞凋亡减少 ,造成细胞堆积 ,参与肺血管结构改建 ,是肺动脉高压形成机制之一。

Objective: To study the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to congenital heart disease. Methods: Terminal deoxynuleotidyl transferase mediated uUTP nick end labeling(TUNEL) technique was used to detect nucleosomal DNA fragmentation of apoptotic cells and immunohistochemial technique for the detection of proliferation cells in the pulmonary artery wall. Also immunohistochemical technique was used for the detection of expression level of bcl 2 and bax protein in the artery wall. Results: The pulmonary artery wall of CHD group become incrassate than control group. Proliferative and apoptotic cells can be found in both CHD group and control group but proliferative index of CHD group increased significantly and apoptotic index decreased significantly than control group. Through the methods of immunohistochemical, we found the expression of bcl 2 increased whereas bax decreased significantly in the artery wall of CHD group. Conclusion: The abnormal expression of bcl 2 and bax induced by CHD play important role in the pulmonary artery remodeling which is the main pathology change of pulmonary hypertension secondary to CHD.