Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Respir Physiol Neurobiol. 2010 Sep 30;173(2):179-88. doi: 10.1016/j.resp.2010.08.005. Epub 2010 Aug 12.
We tested the hypothesis that at the early phase of acute lung injury (ALI) the degree of endothelium injury may predict lung parenchyma remodelling. For this purpose, two models of extrapulmonary ALI induced by Escherichia coli lipopolysaccharide (ALI-LPS) or cecal ligation and puncture (ALI-CLP) were developed in mice. At day 1, these models had similar degrees of lung mechanical compromise, epithelial damage, and intraperitoneal inflammation, but endothelial lesion was greater in ALI-CLP. A time course analysis revealed, at day 7: ALI-CLP had higher degrees of epithelial lesion, denudation of basement membrane, endothelial damage, elastic and collagen fibre content, neutrophils in bronchoalveolar lavage fluid (BALF), peritoneal fluid and blood, levels of interleukin-6, KC (murine analogue of IL-8), and transforming growth factor-β in BALF. Conversely, the number of lung apoptotic cells was similar in both groups. In conclusion, the intensity of fibroelastogenesis was affected by endothelium injury in addition to the maintenance of epithelial damage and intraperitoneal inflammation.
我们检验了这样一个假说,即在急性肺损伤(ALI)的早期阶段,内皮细胞损伤的程度可能可以预测肺实质的重塑。为此,我们在小鼠中建立了两种由大肠杆菌脂多糖(ALI-LPS)或盲肠结扎穿孔(ALI-CLP)引起的肺外 ALI 模型。在第 1 天,这些模型具有相似程度的肺机械功能障碍、上皮损伤和腹腔内炎症,但 ALI-CLP 中的内皮损伤更大。时间进程分析显示,在第 7 天:ALI-CLP 具有更高程度的上皮损伤、基底膜剥脱、内皮损伤、弹性纤维和胶原纤维含量、支气管肺泡灌洗液(BALF)、腹腔液和血液中的中性粒细胞、白细胞介素-6(IL-6)、KC(鼠源 IL-8 类似物)和转化生长因子-β在 BALF 中的水平。相反,两组肺细胞凋亡的数量相似。总之,除了维持上皮损伤和腹腔内炎症外,成纤维弹性生成的强度还受到内皮细胞损伤的影响。