Bcl-2和Bax在吸烟诱导大鼠肺血管重建中的作用研究

摘要

Objective It is to approach the action of Bel - 2 and Bax in pneumoangiogram restitution of rat induced with smoking. Methods Chronic smoking exposure rat models were established. Mean pulmonary artery pressure ( mPAP ) was measured with right cardiac catheterization. Right ventricular hypertrophy index was calculated. The constituent ratios of CMA, PMA and NMA were calculated with HE staining. The expressions of SM - a - actin, Bel - 2 protein and Bax protein in pulmonary small artery were detected with immunohistochemical method. The expressions of Bel - 2 mRNA, Bax mRNA in pulmonary small artery were detected with RT - PCR method. Results The mPAP in smoking groups were both higher than that in normal control group ( both P <0.01 ). Smoking could cause right ventricular hypertrophy ( P <0.01 ) and the differences were more significant with the prolongation of experiment ( P < 0.05 ). The percentage of CMA and the expressions of SM -a. - actin, Bel -2 protein and Bel -2 mRNA in smoking groups were all higher than those in normal control group ( all P <0. 05 ), and the expressions of Bax protein and Bax mRNA and the ratios of Bax mRNA/Bcl - 2 mRNA, Bax/Bcl - 2 in smoking groups were all significantly lower than those in normal control group ( all P < 0. 01 ). Moreover, the lowered of the ratios of Bax mRNA/Bcl - 2 mRNA and Bax/Bcl - 2 in smoking groups were more significant with the prolongation of experiment ( both P <0. 05 ). Through rectilinear correlation analysis, all the expression of SM - a - actin were positively related to the expressions of Bel - 2 mRNA ( all P < 0.01 ), but negatively related to the expressions of Bax mRNA ( all P < 0. 05 ). Conclusion Chronic smoking can induce pneumoangiogram restitution, pulmonary hypertension, the abnormal expressions of Bel - 2 and Bax and the dysequilibrium of Bax/Bcl - 2. The dysequilibrium of Bax/Bcl - 2 maybe one of the mechanisms of smoking inducing pulmonary artery smooth muscle cell proliferation, pneumoangiogram restitution and pulmonary hypertension formation.%目的 探讨Bcl-2和Bax在吸烟诱导大鼠肺血管重建中的作用.方法 制备大鼠慢性吸烟动物模型;右心导管法测定并记录肺动脉平均压(mPAP);计算右心室肥厚指数(RV/(LV+S));HE染色计算腺泡内环肌型动脉(CMA)、部分肌型动脉(PMA)和非肌型血管(NMA)3种类型血管的构成比;免疫组织化学方法检测肺小动脉SM-α-actin、Bcl-2蛋白及Bax蛋白的表达;采用逆转录-聚合酶链反应(RT-PCR)方法检测肺小动脉Bcl-2 mRNA、Bax mRNA的表达.结果 吸烟组大鼠mPAP均高于正常对照组(P均<0.01);吸烟能明显引起右心室肥厚(P<0.01),且随时间的延长差异更显著(P<0.05);吸烟组大鼠CMA占血管总数的百分值、肺小动脉SM-α-actin、Bcl-2蛋白、Bcl-2 mRNA表达均高于正常对照组(P均<0.05),Bax蛋白、Bax mRNA表达及Bax mRNA/Bcl-2 mRNA、Bax/Bcl-2比值均显著低于正常对照组(P均<0.01),并随时间的延长吸烟组Bax mRNA/Bcl-2 mRNA、Bax/Bcl-2比值降低均更显著(P均<0.05).直线相关分析发现各组大鼠SM-α-actin与Bcl-2 mRNA均呈正相关(P均<0.01),与Bax mRNA均呈负相关(P均<0.05).结论 慢性吸烟可导致肺血管重建、肺动脉高压、肺动脉Bcl-2和Bax的表达异常和Bax/Bcl-2平衡失调,Bax/Bcl-2平衡失调可能是吸烟引起肺动脉平滑肌细胞增殖、肺血管重建及肺动脉高压形成的机制之一.