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。%[ ABSTRACT] AIM:To observe the effects of long-term cigarette smoke exposure on pulmonary vascular remode-ling 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 andα-smooth muscle actin staining were performed to observe the pul-monary vascular remodeling.The protein expression of proliferating cell nuclear antigen ( PCNA) and TGF-β1 in the pulmo-nary 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-12W group ( P<0.01) .Significant increases in the protein expression of PCNA and TGF-β1 in smoke exposure groups were ob-served 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-12W groups (P<0.05).The mRNA expression of TGF-β1 was positively correlated with pulmonary vascular muscularization, WT% and the protein expression of PCNA.CONCLU-SION: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.
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