特发性肺纤维化患者肺组织中窖蛋白-1和细胞外基质的表达

Expressions of caveolin-1 and extracellular matrix in lung tissues of patients with idiopathic pulmonary fibrosis

目的研究特发性肺纤维化（IPF）患者肺组织窖蛋白一1和细胞外基质表达的变化及其意义。方法6例IPF患者的肺组织标本来自2005年1月至2008年12月南京大学医学院附属鼓楼医院呼吸科住院患者，其开胸肺活检组织病理诊断符合普通型间质性肺炎。6例肺癌患者行肺叶切除，取其远离病变的肺组织标本作为对照组。用RT—PCR、Westernblot及免疫组织化学方法检测肺组织标本中的窖蛋白-1mRNA和蛋白表达。Westernblot检测肺组织标本的胶原-I、α-平滑肌肌动蛋白（α-SMA）和Smads蛋白表达。结果IPF患者肺组织窖蛋白-1的mRNA和蛋白表达（分别为0．05±0．02和0．16±0．05）明显低于对照组（分别为0．66±0．19和0．81±0．11），差异有统计学意义（F值分别为8．465和353．836，均P〈0．05）。IPF患者肺组织的胶原．I（0．85±0．11）和d—SMA蛋白（0．784-0．08）表达明显高于对照组（分别为0．164-0．04和0．14±0．05），差异有统计学意义（F值分别为485．09、410．027，均P〈0．05）。IPF患者肺组织的p-Smad2蛋白（0．78±0．08）和p-Smad3蛋白（0．86±0．07）表达明显高于对照组（分别为0．17±0．04和0．14±0．04），差异有统计学意义（F值分别为521．97和530．48，均P〈0．05）；而Smad7蛋白表达（0．22±0．05）明显低于对照组（0．78±0．08），差异有统计学意义（F=414．84，P〈0．05）。结论IPF患者肺组织窖蛋白-1表达下调与特发性肺纤维化的发牛和发展有关。

Objective To investigate the expressions of caveolin-1, collagen- I , α-smooth muscle actin（α-SMA） and Smad in lung tissues of patients with idiopathic pulmonary fibrosis （IPF） and therefore to explore their potential roles in the pathogenesis of the disease. Methods Six patients with IPF confirmed pathologically by open lung biopsy in Department of Pulmonary Medicine, Affiliated Drum Tower Hospital of Nanjing University from January 2005 to December 2008 were studied. Diagnosis of IPF was made in accordance with the American Thoracic Society/European Respiratory Society Consensus Statement. At the same period, 6 normal lung samples were also obtained from patients with lung cancer by surgical resections as the control group. The level of caveolin-1 mRNA and protein, collagen- I , α-SMA and Smads in lung tissues were detected by RT-PCR, Western blot and immunohistochemistry. Results Compared with the control group, significantly reduced levels of caveolin-1 mRNA and protein （0. 66 ± 0. 19 vs 0. 05 ± 0. 02 ; 0. 81 ±0. 11 vs 0. 16 ±0. 05 ,P 〈0. 05） were observed in the lungs of patients with IPF. However, collagen-1 （0. 85 ±0. 11 vs 0. 16 ± 0.04） and ct-SMA（0. 78 ±0.08 vs 0. 14 ±0.05） proteins in the lung tissues of IPF patients were significantly increased as compared to the controls （P 〈 0. 05 ）. The expressions of p-Smad2 and p-Smad3 proteins were significantly increased （0. 78 ±0. 08 vs 0. 17 ±0. 04;0. 86 ±0. 07 vs 0. 14 ±0. 04, respectively, P 〈0.05）, while that of smad7 protein decreased （0. 22 ±0. 05 vs 0. 78 ±0. 08 ,P 〈0. 05） in the lungs of patients with IPF as compared with the control groups. Conclusion The reduced expression of caveolin-1 in lung tissues of IPF may be related to the development and progress of pulmonary fibrosis.