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骨髓间充质干细胞减轻光气诱导的大鼠急性肺损伤。

Bone marrow-derived mesenchymal stem cells attenuate phosgene-induced acute lung injury in rats.

作者信息

Chen Junfeng, Shao Yiru, Xu Guoxiong, Lim ChitChoon, Li Jun, Xu Daojian, Shen Jie

机构信息

Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University , Shanghai , China .

出版信息

Inhal Toxicol. 2015;27(5):254-61. doi: 10.3109/08958378.2015.1037029. Epub 2015 May 13.

Abstract

Accidental phosgene exposure could result in acute lung injury (ALI), effective therapy is needed for the patients with phosgene-induced ALI. As a type of cells with therapeutic potential, mesenchymal stem cells (MSCs) have been showed its efficacy in multiple diseases. Here, we assessed the therapeutic potential of MSCs in phosgene-induced ALI and explored the related mechanisms. After isolation and characterization of rat bone marrow MSCs (BMMSCs), we transplanted BMMSCs into the rats exposed to phosgene and observed significant improvement on the lung wet-to-dry ratio and partial oxygen pressure (PaO2) at 6, 24, 48 h after phosgene exposure. Histological analyses revealed reduced sign of pathological changes in the lungs. Reduced level of pro-inflammatory tumor necrosis factor α and increased level of anti-inflammatory factor interleukin-10 were found in both bronchoalveolar lavage and plasma. Significant increased expression of epithelial cell marker AQP5 and SP-C was also found in the lung tissue. In conclusion, treatment with MSC markedly decreases the severity of phosgene-induced ALI in rats, and these protection effects were closely related to the pulmonary air blood barrier repairment and inflammatory reaction regulation.

摘要

意外接触光气可导致急性肺损伤(ALI),光气诱导的ALI患者需要有效的治疗方法。间充质干细胞(MSCs)作为一种具有治疗潜力的细胞,已在多种疾病中显示出其疗效。在此,我们评估了MSCs对光气诱导的ALI的治疗潜力,并探讨了相关机制。在分离和鉴定大鼠骨髓间充质干细胞(BMMSCs)后,我们将BMMSCs移植到暴露于光气的大鼠体内,并观察到在光气暴露后6、24、48小时肺干湿比和动脉血氧分压(PaO2)有显著改善。组织学分析显示肺组织病理变化迹象减轻。在支气管肺泡灌洗和血浆中均发现促炎肿瘤坏死因子α水平降低,抗炎因子白细胞介素-10水平升高。肺组织中上皮细胞标志物水通道蛋白5(AQP5)和表面活性蛋白C(SP-C)的表达也显著增加。总之,MSCs治疗可显著降低大鼠光气诱导的ALI严重程度,这些保护作用与肺气血屏障修复和炎症反应调节密切相关。

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