bcl-2/bax表达在左向右分流型肺动脉高压肺血管重构中的作用

Role of bcl-2 and bax expressions in pulmonary vascular remodeling of PAH rats secondary to left-right shunt CHD

目的研究bcl-2、bax蛋白表达与左向右分流型肺动脉高压肺血管重构的关系。方法建立左向右分流肺动脉高压大鼠模型。比较肺血管重构指标,原位杂交和Western blot检测bcl-2和bax分布及表达,TUNEL法检测肺血管细胞的凋亡。结果分流12周和16周组大鼠的平均肺动脉压力(mPAP)、右室肥大指数(RVHI)、肺小动脉中膜厚度百分比(MT%)明显高于正常大鼠(P<0.05),肺小动脉新生内膜比率显著增加(P<0.01)。bcl-2蛋白表达在分流12周后明显增强,分流至16周时表达最高峰(P<0.01),而bax蛋白表达显著降低(P<0.01)。bcl-2/bax呈上升趋势。结论bcl-2和bax在肺动脉上均有表达,随着bcl-2和bax比值的上调,肺血管发生重构,bcl-2/bax比值失衡可能是大鼠左向右分流PAH形成的机制之一。

Objective To investigate the roles of the expressions of B cell lymphoma-2 （bcl-2） and Bclassosiated X （bax） in the pulmonary vascular remodeling （PVR） of pulmonary arterial hypertension （PAH） secondary to left-right shunt congenital heart disease （CHD）. Methods A total of 80 SPF SD rats were randomly divided into 8 groups, shunt groups （ S Ⅰ, S Ⅱ , SllI and S IV） and control groups （ C Ⅰ , C Ⅱ , C Ⅲ and C Ⅳ）. PAH rat model was established in the shunt groups by left-to-fight shutting, and the control groups received sham operation. The rats from Ⅰ , Ⅱ, Ⅲ and Ⅳ groups were sacrificed in 4, 8, 12 and 16 weeks after operation. Mean pulmonary arterial pressure （mPAP） was recorded. Pathologic observations were made to assess pulmonary vascular remodeling. Their lung tissues were detected by in situ hybridization histochemistry （ISHH） technique and Western blotting for bcl-2 and bax. And apoptosis of pulmonary artery smooth muscle cells （PSMCs） and endothelial cells （ECs） were also detected by TUNEL. Results After 12 weeks or 16 weeks shunt, following indexes of the shunt groups were significantly higher than the control groups （P 〈 0. 05, 0.01 ）, such as mPAP, right ventricular hypertrophy index （RVHI）, percentage of small pulmonary arteries media thickness （ MT% ） , and ratio of neointimal formation in pulmonary arterioles. The expression of bcl-2 protein were significantly increased after 16 weeks＇ shutting （P 〈0. 01 ）, but bax was significantly decreased （ P 〈 0. 01 ）, bcl-2/bax was significantly increased with the tendency of bcl-2. Conclusion bcl-2 and bax are expressed in pulmonary artery. The ratio of bcl-2/bax plays an important role in proceeding of PVR in PAH induced by left-right shunting, and its elevation seems related to the development of pulmonary vascular remodeling during PAH, and possibly is involved in PVR.