凋亡机制在风湿性心脏病二尖瓣狭窄肺动脉高压形成中的作用

Apoptosis Relative Mechanism in the Pulmonary Hypertension Secondary to Rheumatic Heart Disease

目的：研究凋亡机制在风湿性心脏病单纯二尖瓣狭窄(RHD MS)所致肺动脉高压(PH)形成机制中的作用。方法：应用免疫组化 及原位缺口末端 DNA 标记技术检测风湿性心脏病二尖瓣狭窄重度肺动脉高压者肺动脉活检标本，检测肺动脉血管壁细胞的增殖、凋亡 情况。用免疫组化技术检测凋亡相关基因 bc1-2和 bax 的表达。结果：RHD 患者肺动脉的结构发生明显改建，RHD 及对照组肺动脉内 都有增殖与凋亡的细胞，但 RHD 组增殖细胞多而凋亡细胞明显减少。bcl-2在 RHD 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 RHD 组。结论：在肺血淤滞、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，参与引起肺血管结构改建，从而参与导致肺动脉高压。

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