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骨髓间充质干细胞对脂多糖致大鼠肺冲击伤合并内毒素血症的治疗作用。

Therapeutic effects of bone marrow-derived mesenchymal stem cells on pulmonary impact injury complicated with endotoxemia in rats.

机构信息

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing 400042, China.

出版信息

Int Immunopharmacol. 2013 Feb;15(2):246-53. doi: 10.1016/j.intimp.2012.12.008. Epub 2012 Dec 26.

Abstract

Previous studies have demonstrated that acute lung injury (ALI) is associated with significant mortality and so far no effective pharmacotherapy is shown to reverse the natural progression. This study aims to investigate whether the transplantation of bone marrow derived mesenchymal stem cells (MSCs) might restore damaged pulmonary function and tissue structure in ALI. By using a sublethal chest impact injury plus endotoxemia model, MSCs were intravenously transplanted into the injured rats 2h after trauma. The blood samples were obtained for determination of blood gas. Bronchoalveolar lavage fluid (BALF) was collected for analysis of inflammatory cell count and cytokine (TNF-α, IL-1β, IL-6 and IL-10) levels. The left lower lobes of the lungs, nearby the impact zone, were collected for SRY gene analysis and histological examination and scoring. After engraftment of MSCs, the number of inflammatory cells in BALF was decreased. Meanwhile, the secretions of pro-inflammatory TNF-α and IL-6 were alleviated, while the secretion of anti-inflammatory IL-10 was elevated. Engraftment of MSCs improved the pulmonary gas exchanges, alleviated the lung injury, and reduced the rats' mortality. These results suggested that the MSCs based measures might be a promising strategy in trauma and endotoxemia induced ALI treatment.

摘要

先前的研究表明,急性肺损伤(ALI)与显著的死亡率相关,到目前为止,还没有显示出有效的药物治疗可以逆转其自然进展。本研究旨在探讨骨髓间充质干细胞(MSCs)移植是否可能恢复 ALI 中受损的肺功能和组织结构。通过使用亚致死性胸部撞击伤加内毒素血症模型,在创伤后 2 小时将 MSCs 静脉内移植到受伤的大鼠中。采集血样以确定血气。收集支气管肺泡灌洗液(BALF)以分析炎性细胞计数和细胞因子(TNF-α、IL-1β、IL-6 和 IL-10)水平。采集左肺下叶(靠近撞击区)进行 SRY 基因分析和组织学检查和评分。MSCs 移植后,BALF 中的炎性细胞数量减少。同时,促炎 TNF-α和 IL-6 的分泌得到缓解,而抗炎性 IL-10 的分泌增加。MSCs 的移植改善了肺气体交换,减轻了肺损伤,并降低了大鼠的死亡率。这些结果表明,基于 MSCs 的措施可能是创伤和内毒素血症诱导的 ALI 治疗的一种有前途的策略。

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