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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 study the relationship between bcl-2, bax protein expression and pulmonary vascular remodeling in left-to-right shunt pulmonary hypertension. Methods A rat model of left pulmonary artery bypass grafting was established. The indexes of pulmonary vascular remodeling were compared, the distribution and expression of bcl-2 and bax were detected by in situ hybridization and Western blot, and the apoptosis of pulmonary vascular cells was detected by TUNEL method. Results The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI) and percentage of pulmonary arterioles (MT%) in shunting groups at 12 and 16 weeks were significantly higher than those in normal rats (P <0.05) The ratio of neointima to arterioles increased significantly (P <0.01). The expression of bcl-2 protein increased significantly at 12th week of shunt, and peaked at 16th week (P <0.01), while the expression of bax protein decreased significantly (P <0.01). bcl-2 / bax is on the rise. Conclusions Both bcl-2 and bax are expressed in pulmonary arteries. With the increase of bcl-2 and bax ratio, the remodeling of pulmonary vessels may occur. The imbalance of bcl-2 / bax ratio may be the mechanism of the formation of left to right shunt PAH in rats one.