Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen
Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen
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脂多糖三击方案诱导急性肺损伤引起的快速肺纤维化
DOI：
10.1177/1753425908101509
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发表时间：
2009-06-01
期刊：
影响因子：
3.2
通讯作者：
Yao, Zhibin
中科院分区：
文献类型：
--
作者：
Li, Hui;Du, Shaohui;Yao, Zhibin
根据严重急性呼吸综合征（SARS）和高致病性禽流感的共同特点以及炎症和纤维化的发生机制，推测SARS冠状病毒、H5 N1病毒等多种病因或其他未知因素导致严重急性肺损伤（ALI）导致的快速肺纤维化是一个基本的病理规律，以及脂多糖（LPS），最常见的致病因素。本研究采用气管内、腹腔内和气管内应用LPS三次打击方案，与博莱霉素诱导的慢性肺纤维化进行比较。通过观察Th 1/Th 2平衡、Sma和MAD相关蛋白（Smads）、信号转导和转录激活因子（STATs）的表达，评价炎症损伤和纤维化的程度，并分析其分子机制。结果提示，ALI可通过LPS三次打击诱导快速肺纤维化。LPS组3-7天是第一个快速肺纤维化阶段，而第二个快速肺纤维化阶段发生在第14-21天。Th 2细胞极化、Smad 4和Smad 7可能是ALI快速纤维化的重要分子机制。本研究不仅为建立一种新的快速肺纤维化模型提供了实验依据，也为进一步探讨急性肺损伤向快速肺纤维化转化的机制提供了理论依据。
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.