Krebs Joerg, Kolz Alexander, Tsagogiorgas Charalambos, Pelosi Paolo, Rocco Patricia R M, Luecke Thomas
Department of Anaesthesiology and Critical Care Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany.
Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino - IST, University of Genoa, Genoa, Italy.
Respir Physiol Neurobiol. 2015 Jul;212-214:25-32. doi: 10.1016/j.resp.2015.04.003. Epub 2015 Apr 9.
This study aimed to assess the impact of pulmonary inflammation on early fibrotic response in rats challenged with increasing doses of lipopolysaccharide (LPS). Twenty-four rats were randomized and infused with three different increasing doses of continuous LPS infusion (n=8/group) while being ventilated with low tidal volumes and open-lung positive end-expiratory pressure. Another eight animals served as uninjured control group. Hemodynamics, gas exchange, respiratory system mechanics, lung histology, α-smooth muscle actin, plasma cytokines, and mRNA expression of cytokines and type I and III procollagen in lung tissue were assessed. We found impaired hemodynamics and gas exchange as well as higher histological lung injury scores and α-smooth muscle actin expressions in the medium LPS dose compared to control and the lower LPS dose. The highest LPS dose did not cause further aggravation of these findings. In all LPS groups type I and III procollagen decreased compared to controls and there was a negative correlation between type III procollagen-RNA expression and proinflammatory mediators.
本研究旨在评估在接受递增剂量脂多糖（LPS）刺激的大鼠中，肺部炎症对早期纤维化反应的影响。将24只大鼠随机分组，以三种不同的递增剂量持续输注LPS（每组n = 8只），同时采用低潮气量和开放肺呼气末正压通气。另外8只动物作为未受伤的对照组。评估血流动力学、气体交换、呼吸系统力学、肺组织学、α平滑肌肌动蛋白、血浆细胞因子以及肺组织中细胞因子和I型和III型前胶原的mRNA表达。我们发现，与对照组和低LPS剂量组相比，中LPS剂量组存在血流动力学和气体交换受损，以及更高的肺组织学损伤评分和α平滑肌肌动蛋白表达。最高LPS剂量并未导致这些结果进一步加重。与对照组相比，所有LPS组的I型和III型前胶原均减少，且III型前胶原RNA表达与促炎介质之间存在负相关。
