Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice
Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice
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Obaculactone 可预防博莱霉素诱导的小鼠肺纤维化
DOI：
10.1016/j.taap.2016.05.005
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发表时间：
2016
影响因子：
3.8
通讯作者：
Xu Qiang
中科院分区：
文献类型：
--
作者：
Wang Xingqi;Ouyang Zijun;You Qian;He Shuai;Meng Qianqian;Hu Chunhui;Wu Xudong;Shen Yan;Sun Yang;Wu Xuefeng;Xu Qiang
特发性肺纤维化是一种进行性、退行性和几乎不可逆的疾病。由于肺纤维化导致的肺损伤几乎没有有效的治疗方法。本研究的目的是评估obaculactone的作用，在已经评估的特发性肺纤维化模型博莱霉素管理诱导。对小鼠进行博莱霉素的气管内滴注，并在每天滴注博莱霉素后口服给予杆菌内酯，持续23天。obaculactone治疗改善体重减轻，肺组织病理学异常和肺胶原沉积，减少支气管肺泡灌洗液中的炎性细胞数量和细胞因子水平。此外，obaculactone抑制表达icam 1，vcam 1，inos和cox 2，并减弱博莱霉素处理的肺氧化应激。重要的是，在obaculactone处理后，肺组织中I型胶原和α-SMA的产生以及肺匀浆中TGF-β1、ALK 5、p-Smad 2和p-Smad 3的水平也降低。TGF-β1诱导的上皮-间充质转化通过Smad依赖和非依赖途径被obaculactone逆转。总的来说，这些数据表明，obaculactone可能是一个有前途的候选药物治疗特发性肺纤维化。
Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression oficam1,vcam1,inosandcox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transitionviaSmad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis.