Survivin在先天性心脏病肺动脉高压发生机制中的作用

目的 研究抗凋亡因子存活素(survivin)在左向右分流性先天性心脏病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,检测肺组织细胞凋亡情况.用免疫组化及Western blot检测凋亡相关蛋白survivin、bcl-2和bax的表达.结果 中、重度肺动脉高压患者肺组织血管的结构发生明显改建;先天性心脏病肺组织都有凋亡的细胞,但中、重度肺动脉高压患者凋亡细胞明显减少.Survivin、bcl-2在中、重度肺动脉高压组中表达强度明显增高,而bax表达明显减少.Survivin与凋亡及肺血管组织结构重构有明显的相关性.结论 在左向右分流血流作用下,Survivin等基因表达发生变化,使肺组织细胞凋亡减少,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.

Role of survivin in pulmonary hypertension of congenital heart disease

Objective To study the role of survivin in the incidence of pulmonary hypertension secondary to congenital heart disease (CHD) of left-to-right shunt. Methods Forty-nine cases were divided into 4 groups according to mean pulmonary artery pressure (mPAP), that is, non-hypertension group, mild hypertension group, medium hypertension group, and severe hypertension group. Their lung tissue samples were collected during heart surgery. TUNEL technique and immunohistochemical analysis were respectively used to detect nuclear DNA fragment of apoptotic cells and the expression of survivin, bcl-2 and bax. Western blotting also was conducted to detect survivin expression. Results The pulmonary wall of CHD patients with medium or severe pulmonary hypertension became significant incrassate. The apoptotic index and expression level of bax were significantly decreased but surviving and bcl-2 expressions were significantly increased in CHD with medium or severe pulmonary hypertension. Survivin expression was significant correlation with percentage media wall thickness and apoptotic index. Conclusion Apoptosis associated with survivin plays an important role in pulmonary artery remodeling after pulmonary hypertension of CHD.