Yin Xiuru, Liang Zuodi, Yun Yue, Pei Ling
Department of Anesthesiology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Cell Physiol Biochem. 2015;35(6):2149-58. doi: 10.1159/000374020. Epub 2015 Apr 7.
BACKGROUND/AIMS: Acute lung injury (ALI) and its aggressive stage, acute respiratory distress syndrome (ARDS), are characterized by diffuse damage and increased permeability of the endothelial barrier, leading to alveolar infiltrates and interstitial edema. Enhancing endothelial integrity represents a novel therapeutic strategy for ALI/ARDS. Endothelial progenitor cells (EPCs) have been reported to participate in endothelial repair of ALI and also serve as a tool for gene therapy. Further, bone morphogenetic protein 2 (BMP2) is an essential signaling molecule that regulates the fate of different cell types. The aim of our study is to explore whether bone marrow-derived EPCs transduced with lentiviral-mediated BMP2 gene might benefit lipopolysaccharide (LPS)-induced ALI in a rat model.
Rats were divided randomly into five groups. The sham group was given normal saline via the trachea and right jugular vein. The other four groups underwent intratracheal-LPS-induced ALI followed after 30 min by treatment with either normal saline, EPCs, EPCs transduced with empty lentiviral vector (EPCs-null), or EPCs transduced with BMP2 (EPCs-BMP2) via the right jugular vein.
We found that the lung injury score, oxygenation, and inflammatory response were significantly ameliorated in the three EPC-treated groups (EPCs, EPCs-null, and EPCs-BMP2). In addition, EPCs-BMP2 further improved endothelium repair and capillary permeability, causing markedly reduced wet-to-dry lung-weight ratio and BALF protein content, and increased levels of BMP2 protein, BMP2 mRNA, and eNOS protein in lung tissues.
Transplantation of BMP2-transduced EPCs effectively attenuates edema and protein exudation compared with EPCs alone in LPS-induced ALI via enhanced expression of BMP2 and eNOS.
背景/目的：急性肺损伤（ALI）及其严重阶段急性呼吸窘迫综合征（ARDS）的特征是内皮屏障的弥漫性损伤和通透性增加，导致肺泡浸润和间质水肿。增强内皮完整性是ALI/ARDS的一种新治疗策略。据报道，内皮祖细胞（EPCs）参与ALI的内皮修复，也是基因治疗的一种工具。此外，骨形态发生蛋白2（BMP2）是调节不同细胞类型命运的重要信号分子。我们研究的目的是探讨慢病毒介导的BMP2基因转导的骨髓源性EPCs是否对脂多糖（LPS）诱导的大鼠ALI模型有益。
将大鼠随机分为五组。假手术组经气管和右颈静脉给予生理盐水。其他四组经气管内注射LPS诱导ALI，30分钟后经右颈静脉分别给予生理盐水、EPCs、空慢病毒载体转导的EPCs（EPCs-空载体）或BMP2转导的EPCs（EPCs-BMP2）。
我们发现三个EPC治疗组（EPCs、EPCs-空载体和EPCs-BMP2）的肺损伤评分、氧合和炎症反应均显著改善。此外，EPCs-BMP2进一步改善了内皮修复和毛细血管通透性，导致肺湿干重比和支气管肺泡灌洗液（BALF）蛋白含量显著降低，肺组织中BMP2蛋白、BMP2 mRNA和内皮型一氧化氮合酶（eNOS）蛋白水平升高。
与单独的EPCs相比，BMP2转导的EPCs移植通过增强BMP2和eNOS的表达，有效减轻了LPS诱导的ALI中的水肿和蛋白渗出。
