长期烟雾暴露对大鼠肺血管重塑及转化生长因子-β1表达的影响  

Effects of long-term cigarette smoke exposure on pulmonary vascular remodeling and TGF-β1 expression in rat pulmonary vessels

作　　者：彭红星[1] 杨荣时[1] 王焕[1] 曾玉兰[1] 

机构地区：[1]华中科技大学同济医学院附属梨园医院呼吸内科,湖北武汉430077

出　　处：《中国病理生理杂志》2016年第7期1327-1330,1335,共5页Chinese Journal of Pathophysiology

基　　金：湖北省自然科学基金资助项目(No.2013CFB078)

摘　　要：目的:观察长期吸烟对大鼠肺血管重塑及转化生长因子-β1(TGF-β1)的影响,探讨其发生的可能机制。方法:将36只健康SD雄性大鼠随机分为对照组、烟雾暴露2周(S-2W)和烟雾暴露12周(S-12W)组。苏木精-伊红染色和α-平滑肌肌动蛋白染色切片观察肺血管重塑的程度,免疫组化法检测增殖细胞核抗原(PCNA)和TGF-β1在肺动脉的相对表达;RT-qPCR检测肺动脉TGF-β1的mRNA表达。结果:随烟雾暴露时间延长,模型组血管壁厚度和血管直径比值(WT%)和完全肌化血管比例均较对照组明显增大,差异具有统计学显著性(P<0.01)。模型组的PCNA及TGF-β1蛋白表达水平均较对照组增大,且两模型组之间差异有统计学显著性(P<0.01)。与对照组比较,模型组TGF-β1的mRNA表达均显著增加(P<0.05),其中S-2W组和S-12W组之间的差异亦有统计学显著性(P<0.05)。TGF-β1的mRNA表达与WT%和完全肌化血管比例呈显著正相关(P<0.01);TGF-β1的mRNA表达与PCNA蛋白表达呈显著正相关(P<0.01)。结论:长期烟雾暴露可导致大鼠肺血管重塑的形成,其机制可能与吸烟上调大鼠肺血管TGF-β1的mRNA表达,诱导肺血管平滑肌细胞增殖有关。AIM： To observe the effects of long-term cigarette smoke exposure on pulmonary vascular remodeling and the protein expression of transforming growth factor-β1（ TGF-β1） in the rats,and to explore the mechanism.METHODS： SD rats（ n = 36） were randomly divided into control group,2-week smoke exposure（ S-2W） group and 12-week smoke exposure（ S-12W） groups. HE staining and α-smooth muscle actin staining were performed to observe the pulmonary vascular remodeling. The protein expression of proliferating cell nuclear antigen（ PCNA） and TGF-β1 in the pulmonary arteries was determined by the method of immunohistochemistry. The mRNA expression of TGF-β1 in the pulmonary arteries was evaluated by RT-qPCR. RESULTS： Compared with control group,ratio of pulmonary vessel wall thickness to vessel diameter（ WT%） and percentage of muscularized vessels were significantly increased in S-2W group and S-12 W group（ P〈0. 01）. Significant increases in the protein expression of PCNA and TGF-β1 in smoke exposure groups were observed compared with control group. There was significant difference between 2 model groups（ P〈0. 01）. Compared with control group,the mRNA expression of TGF-β1 in pulmonary artery walls obviously increased in smoke exposure groups.There was significantly difference between S-2W and S-12 W groups（ P〈0. 05）. The mRNA expression of TGF-β1 was positively correlated with pulmonary vascular muscularization,WT% and the protein expression of PCNA. CONCLUSION： Long-term cigarette smoke exposure results in pulmonary artery remodeling in rats. The possible mechanism is that cigarette smoking exposure induces the over-expression of TGF-β1 at mRNA level in pulmonary vessels and promotes the proliferation of pulmonary vascular smooth muscle cells in rats.

关 键 词：烟雾 肺血管重塑 转化生长因子-Β1 平滑肌 

分 类 号：R363.2[医药卫生—病理学]