中文摘要：

目的探讨阿托伐他汀对实验性肺纤维化的干预作用及机制。方法将C57BL／6小鼠随机分为对照组、博莱霉素组和阿托伐他汀组，博莱霉素组和阿托伐他汀组一次性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，对照组注入等量生理盐水。阿托伐他汀组在气管滴注博莱霉素后每日1次灌胃给予阿托伐他汀10mg·kg^-1·d^-1。分别于术后第3、14及28d处死动物，采用HE染色、Masson染色方法观察肺组织病理变化以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Kruppel样因子4（KLF4）mRNA和蛋白表达水平，以及明胶酶谱分析法检测各组肺组织基质金属蛋白酶2（MMP-2）的活性。结果（1）博莱霉素造模后，小鼠肺组织第3d表现为急性炎症，第14d胶原沉积加重，肺泡结构破坏，第28d肺泡结构、炎症程度及胶原沉积较第14d减轻。阿托伐他汀组各时间点炎症程度和胶原沉积较博莱霉素组均明显减轻。（2）阿托伐他汀组各时间点KLF4表达水平明显低于博莱霉素组（P均〈0．05），其中第3d阿托伐他汀组KLF4mRNA表达水平（0．502±0．261）高于博莱霉素组（0．326±O．164，P〈0．05），但其蛋白表达水平（0．048±0．015）低于博莱霉素组（0．130±0．017），差异有统计学意义（P〈0．05）；（3）染博莱霉素后第3d（3．136±1．321）和第14d（3．449±0．356），小鼠肺组织MMP-2活性较对照组（0．983±0．147）明显上调（P〈0．05），而阿托伐他汀干预后两组MMP-2的活性（2．191±0．800，2．506±O．761）明显下调（P〈0．05），差异有统计学意义（P〈0．05）。结论在实验性肺纤维化中，阿托伐他汀可能是通过对KLF4的调节来实现其抗炎和抗纤维化的作用。

英文摘要：

Objective To investigate the effects and mechanism of atorvastatin in the experimental pulmonary fibrosis. Methods Fifty-four C57BL/6 mice were randomly divided into a control group, a bleomycin group and an atorvastatin group. The mice in the bleomycin group and the atorvastatin group received a single dose intratracheal injection of bleomycin （2. 5 mg/kg） ,while the mice in the control group were injected with isodose physiological saline. The mice in the atorvastatin group were treated with atorvastatin 10 mg · kg^-1 · d^-1 by intragastric administration the day after bleomycin instillation. All groups were sacrificed on the day 3,14 and 28, respectively. HE staining and Masson staining were used to detect the architecture of alveolar and the deposition of cellularity and collagen. RT-PCR and immunohistochemical technology were performed to detect the expression of Krtippel like factor 4 （KLF4）. Zymography was used to investigate the activation of matrix metalloproteinase-2 （MMP-2）. Results After the treatment of bleomycin, the lung tissues showed acute inflammation on the day 3, the collagen deposition was more obvious and the architecture of alveolar was destroyed on the day 14. The alveolar structure, the inflammation and collagen deposition were attenuated on the day 28 compared with the day 14. Compared with the bleoroycin group, the inflammation and the collagen deposition were significantly reduced in the atorvastatin group （ P 〈 O. 05）. Compared with bleoroycin group, the expression of KLF4 significantly decreased in the atorvastatin group,although the expression of KLF4 mRNA increased on the day 3 compared with the bleomycin group （0. 502 ±O. 261 vs. O. 326 ± 0. 164, P 〈 O. 05 ）. The expression of KLF4 protein on the day 3 was significantly decreased compared with the bleomycin group （0. 048 ±0. 015 vs. O. 130 sO. 017,P 〈0. 05）. After the intervention of bleomycin, the activation of MMP-2 on the day 3 and 14 significantly increased compared with the control group （