中文摘要：

目的: Plasminogen 使活跃之物 inhibitor-1 (PAI-1 ) 涉及肺的纤维变性的前进。现在的学习被承担与小介入 RNA (siRNA ) 在 silencing PAI-1 表示的肺的纤维变性上检验效果并且估计可能的位于 \O 下面机制。

英文摘要：

Aim： Plasminogen activator inhibitor-1 （PAl-1） is involved in the progression of pulmonary fibrosis. The present study was undertaken to examine the effects on pulmonary fibrosis of silencing PAl-1 expression with small interfering RNA （siRNA） and to assess the possible underlying mechanisms. Methods： Male Wistar rats were subjected to intratracheal injection of bleomycin （BLM, 5 mg/kg, 0.2 mL） to induce pulmonary fibrosis. Histopathological changes of lung tissue were examined with HE or Masson＇s trichrome staining. The expression levels of a-smooth muscle actin （a-SMA）, collagen type-I and type-Ⅲ, caspase-3, as well as p-ERK1/2 and PI3K/Akt in the lung tissue were evaluated using immunohistochemistry and Western blot analysis. The fibroblasts isolated from BLM-induced fibrotic lung tissue were cultured and transfected with pcDNA-PAI-1 or PAl-1 siRNA. The expression level of PAl-1 in the fibroblasts was measured using real time RT-PCR and Western blot analysis. The flbroblast proliferation was evaluated using MTr assay. Results： Intratracheal injection of PAl-1 siRNA （7.5 nmoL/O.2 mL） significantly alleviated alveolitis and collagen deposition, reduced the expression of PAl-l, α-SMA, collagen type-1 and collagen type-Ⅲ, and increased the expression of caspase-3 in BLM-induced fibrotic lung tissue. In consistence with the in vivo results, the proliferation of the cultured fibroblasts from BLM-induced fibrotic lung tissue was inhibited by transfection with PAl-1 siRNA, and accelerated by overexpression of PAl-1 by transfection with pcDNA-PAI-I. The expression of caspase-3 was increased as a result of PAl-1 siRNA transfection, and decreased after transfection with pcDNA-PAI-I. In addition, the levels of p-ERK1/2 and PI3K/Akt in the fibrogenic lungtissue were reduced after treatment with PAl-1 siRNA. Conclusion： The data demonstrate that PAl-1 siRNA inhibits alveolitis and pulmonary fibrosis in BLM-treated rats via inhibiting the proliferation and promoting the apoptosis of fibrobl