Li Hui, Du Shaohui, Yang Lina, Chen Yangyan, Huang Wei, Zhang Rong, Cui Yinghai, Yang Jun, Chen Dongfeng, Li Yiwei, Zhang Saixia, Zhou Jianhong, Wei Zhijun, Yao Zhibin
Department of Anatomy, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Innate Immun. 2009 Jun;15(3):143-54. doi: 10.1177/1753425908101509.
Based on the common characteristic of severe acute respiratory syndrome (SARS) and highly pathogenic avian influenza and the mechanism of inflammation and fibrosis, it is speculated that there should exist a fundamental pathological rule that severe acute lung injury (ALI)-induced rapid pulmonary fibrosis is caused by various etiological factors, such as SARS coronavirus, H5N1-virus, or other unknown factors, and also by lipopolysaccharide (LPS), the most common etiological factor. The investigation employed intratracheally, and intraperitoneally and intratracheally applied LPS three-hit regimen, compared with bleomycin-induced chronic pulmonary fibrosis. Inflammatory damage and fibrosis were evaluated, and the molecular mechanism was analyzed according to Th1/Th2 balance, Sma- and MAD-related proteins (Smads) and signal transducer and activator of transcriptions (STATs) expression. The results suggested that rapid pulmonary fibrosis could be induced by ALI via LPS three-hits. The period from 3-7 days in the LPS group was the first rapid pulmonary fibrosis stage, whereas the second fast fibrosis stage occurred on days 14-21. Th2 cell polarization, Smad4 and Smad7 should be the crucial molecular mechanism of ALI-induced rapid fibrosis. The investigation was not only performed to establish a new rapid pulmonary fibrosis model, but also to provide the elicitation for mechanism of ALI changed into the rapid pulmonary fibrosis.
基于严重急性呼吸综合征（SARS）和高致病性禽流感的共同特征以及炎症和纤维化的机制，推测应该存在一个基本的病理规律，即由各种病因引起的严重急性肺损伤（ALI）导致的快速肺纤维化，这些病因包括SARS冠状病毒、H5N1病毒或其他未知因素，也包括最常见的病因脂多糖（LPS）。该研究采用气管内、腹腔内和气管内应用LPS的三联打击方案，并与博来霉素诱导的慢性肺纤维化进行比较。评估炎症损伤和纤维化情况，并根据Th1/Th2平衡、Sma和MAD相关蛋白（Smads）以及信号转导和转录激活因子（STATs）的表达分析分子机制。结果表明，ALI通过LPS三联打击可诱导快速肺纤维化。LPS组3至7天为第一个快速肺纤维化阶段，而第二个快速纤维化阶段出现在14至21天。Th2细胞极化、Smad4和Smad7应该是ALI诱导快速纤维化的关键分子机制。该研究不仅旨在建立一种新的快速肺纤维化模型，还为ALI转变为快速肺纤维化的机制提供启发。
