姜黄素上调博来霉素诱导肺纤维化C57BL/6小鼠Cathepsin K表达

摘要

This study aimed to investigate the effect of curcumin on the expression of cathepsin K in bleomycin-induced pulmonary fibrosis C57BL/6 mice. Intratracheal application of bleomycin in C57BL/6 mice was conducted. Briefly,tracheas of anaesthetized mice were surgically exposed and 0.025 U of bleomycin diluted in sterile saline or saline only was slowly instilled. The mice were divided into three groups randomly, which were the control group, the bleomycin group, and the bleomycin plus curcumin (200 mg·kg per day) group. From the second day after instillations, mice were challenged with saline or curcumin ( 200 mg· kg per day) in 0.5 ％ carboxymethyl cellulose via oral gavage. The mice were sacrificed at 7, 14 and 28 days post-treatment after pulmonary fibrosis determination by estimating lung collagen content and lung histopathology. In addition, changes in cathepsin K protein levels in the lung were determined by immunohistochemistry, real time RT-PCR and western blotting. The results showed that cathepsin K protein levels were strongly increased in the bleomycin plus curcumin group treated mice compared to only bleomycin treated mice. Moreover, bleomycin plus curcumin group treated mice responded with a lower collagen deposition and inflammation in the lungs, which was accompanied by a significantly higher lung resistance compared to bleomycin-treated mice. In addition, mice in the bleomycin plus curcumin group were responded with a lower degree of lung fibrosis than the bleomycin-treated mice. It is concluded that curcumin via upregulation of cathepsin K expression and reduced lung collagen deposition in response to bleomycin challenge. Thereby, curcumin may partial protect against bleomycin-induced lung fibrosis.%目的:研究姜黄素对博来霉素诱导肺纤维化C<,57BL/6>小鼠Cathepsin K表达的影响.方法:博来霉素气管注射造小鼠肺纤维化模型,随机分为对照组(气管内注入0.1mL生理盐水)、模型组(气管内注入0.025U博来霉素)、姜黄素组(气管内注入0.025U博来霉素);造模后第2d,对照组和模型组给予0.5%羧甲基纤维素钠生理盐水灌胃,姜黄素组给予200 mg·kg<'-1>·d<'-1>姜黄素灌胃,分别于造模后第7、14、28d取材.采用H&E及Mallory染色观察肺组织病理学变化;应用免疫组学Cathepsin K蛋白的表达,经图像分析各组之间的差异.结果:姜黄素组、模型组与对照组比较都有不同程度的炎症及纤维化病灶,但是姜黄素组与对照组比较炎症及纤维化程度明显减轻;姜黄素组、模型组与对照组比较Cathepsin K表达都有不同程度增加,但是姜黄素组与对照组比较Cathepsin K表达显著增加.结论:姜黄素可能是通过增加Cathepsin K的表达从而降解胶原而实现抗纤维化作用.