Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Cell Transplant. 2010;19(8):965-71. doi: 10.3727/096368910X506845. Epub 2010 May 4.
The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups (n = 6 each). In the acute lung injury (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 μg, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 × 10(7) cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance (E(st)), resistive (ΔP(1)), and viscoelastic (ΔP(2)) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelial and endothelial repair with multinucleated type II pneumocytes. These histological changes yielded a reduction in lung E(st), ΔP(1), and ΔP(2) compared to ALI. In the present experimental ALI model, the administration of BMDMC yielded a reduction in the inflammatory process and a repair of epithelium and endothelium, reducing the amount of alveolar collapse, thus leading to an improvement in lung mechanics.
本研究旨在验证骨髓单个核细胞（BMDMC）治疗可改善内毒素诱导的肺损伤中的肺力学和组织学这一假设。24 只 C57BL/6 小鼠被随机分为四组（每组 6 只）。在急性肺损伤（ALI）组中，通过气管内滴注大肠杆菌脂多糖（LPS）（40μg，IT），而对照组（C）小鼠接受生理盐水（0.05ml，IT）。在给予生理盐水或 LPS 1 小时后，静脉注射 BMDMC（2×10(7)个细胞）。在第 28 天，对动物进行麻醉，并分析肺力学[静态弹性（E(st)）、阻力（ΔP(1)）和粘弹性（ΔP(2)）]和组织学（光镜和电镜）。免疫金电子显微镜用于评估多核细胞是否为 II 型上皮细胞。BMDMC 治疗可预防内毒素诱导的肺炎症、肺泡塌陷和间质水肿。此外，BMDMC 给药导致上皮和内皮修复，出现多核 II 型肺泡细胞。与 ALI 相比，这些组织学变化导致肺 E(st)、ΔP(1)和ΔP(2)降低。在本实验性 ALI 模型中，BMDMC 的给药减少了炎症过程，修复了上皮和内皮，减少了肺泡塌陷的数量，从而改善了肺力学。
