中文摘要：

目的探讨博莱霉素诱导小鼠肺纤维化模型中，Krtippel样因子4（KLF4）的表达及其意义。方法C57BL／6小鼠随机分为生理盐水对照组（Contr01）和博莱霉素组（BLM），经气管内注入博莱霉素（2．5mg／kg）建立实验性小鼠肺纤维化模型，注入等量生理盐水作为对照组，分别于术后第12h、1d、2d、3d、7d、14d及28d取材，采用HE染色和Masson染色观察肺组织病理变化及胶原的沉积部位和数量，实时定量PCR法和免疫组织化学法分别检测各组肺组织中KLF4mRNA和蛋白表达水平。结果博莱霉素诱导的小鼠肺纤维化过程中，第1、2及3d表现为急性炎症；第7d炎症加重，并出现胶原沉积；第14d肺泡结构塌陷，胶原沉积明显；第28d肺泡结构基本正常，炎症程度和胶原沉积较轻。与对照组相比，博莱霉素组小鼠肺组织中KLF4mRNA的表达水平第1d开始升高，而后降低，第3d达最低后逐渐升高直至第28d。博莱霉素组小鼠肺组织中KLF4蛋白的表达趋势与mRNA水平基本一致，第1d开始升高，而后降低，第3d达最低后逐渐增加至第14d后再次降低。结论KLF4在博莱霉素致肺纤维化过程中呈现明显的动态变化，并可能参与了肺纤维化的发生与发展。

英文摘要：

Objective To investigate the expression and significance of Krtippel-like factor 4 （KLF4） in the lung tissues of mice with bleomycin-induced pulmonary fibrosis. Methods C57BL/6 mice were randomly divided into a control group and a BLM group. The mice in the BLM group were given a single intratracheal injection of bleomycin （2.5 mg/kg）, while those in the control group were injected with isodose physiological saline. The mice were sacrificed at the 12h and on the day 1,2,3,7,14 and 28,then HE stain and Masson＇ s trichrome stain were used to detect the architecture of alveolar and the deposition of cellularity and collagen. Real time-polymerase chain reaction （RT-PCR） and immunohistochemical technology were performed to investigate the expression of KLF4. Results In the bleomycin-induced pulmonary fibrosis, acute inflammation was observed on the day 1,2 and 3, the inflammation was exacerbated and the collagen deposition began to be observed on the day 7, the architecture of alveolar was destroyed and the collagen deposition was more obvious on the day 14,while the alveolar structure was nearly recovered to normal, and the inflammation and collagen deposition were attenuated on the day 28. The expression of KLF4 mRNA increased from the day 1, then decreased,arrived at the minimum on the day 3,and then gradually increased until the day 28. The trend of KLF4 protein expression showed roughly the same as the KLF4 mRNA level,which started to increase on the day 1, then decreased, arrived at the minimum on the day 3, then gradually increased until the day 14 and then decreased again. Conclusion The expressions of KLFd mRNA and protein are dynamically changed in the process of experimental pulmonary fibrosis, suggesting KLF4 may contribute to the pathogenesis of pulmonary fibrosis.