Bcl-2和Bax在吸烟诱导大鼠肺血管重建中的作用研究

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-2mRNA、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。

Role study of Bcl-2 and Bax in pneumoangiogram restitution of rat induced with smoking

Objective It is to approach the action of Bcl-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-α-actin,Bcl-2 protein and Bax protein in pulmonary small artery were detected with immunohistochemical method.The expressions of Bcl-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-α-actin,Bcl-2 protein and Bcl-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-α-actin were positively related to the expressions of Bcl-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 Bcl-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.