The Mechanisms Involved in Mesenchymal Stem Cell Alleviation of Sepsis-Induced Acute Lung Injury in Mice: A Pilot Study
The Mechanisms Involved in Mesenchymal Stem Cell Alleviation of Sepsis-Induced Acute Lung Injury in Mice: A Pilot Study
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间充质干细胞缓解小鼠脓毒症引起的急性肺损伤的机制：一项初步研究
DOI：
10.1016/j.curtheres.2020.100593
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发表时间：
2020-01-01
影响因子：
1.9
通讯作者：
Luo, Congjuan
中科院分区：
文献类型：
--
作者：
Luo, Feng;Jiang, Wei;Luo, Congjuan
背景：急性肺损伤是重症监护病房脓毒症患者常见的并发症。炎症是脓毒症的主要机制之一。因此，抑制炎症是脓毒症治疗的重要机制。目的：研究间充质干细胞（Mesenchymal stem cells，MSCs）对脓毒症诱导的急性肺损伤（acute lung injury，ALI）的影响。方法：雄性C57 BL/6小鼠行盲肠结扎穿孔术（cecal ligation and puncture，CLP）诱导脓毒症，术后3 h分别给予生理盐水或MSCs（1 × 106个细胞）。评估术后生存率。通过组织学评分、肺水肿、血管通透性、炎性细胞浸润和支气管肺泡灌洗液中细胞因子水平评估肺损伤。最后，我们测试了活化的B细胞在肺tissue.Results活化的核因子κ-轻链增强子：如预期的那样，CLP引起肺损伤的组织病理学评分，肺湿干重比，和总蛋白浓度的显着增加。然而，用MSC治疗的小鼠具有肺组织病理学变化、肺湿干重比和总蛋白浓度的改善。骨髓间充质干细胞治疗后，支气管肺泡灌洗液中的细胞因子肿瘤坏死因子α、白细胞介素6、白细胞介素1 β和白细胞介素17的水平显著降低。与此相反，白细胞介素10的表达增加后，骨髓间充质干细胞治疗。此外，用MSC治疗的小鼠的存活率高于CLP组。骨髓间充质干细胞注射后，支气管肺泡灌洗液中的神经细胞浸润减弱，但在骨髓间充质干细胞组中观察到的巨噬细胞的数量与CLP组相比没有显着差异。此外，骨髓间充质干细胞治疗显着减少核因子κ-轻链增强剂的活化B细胞activationin肺tissue.Conclusions：基于上述研究结果，治疗骨髓间充质干细胞抑制炎症反应，抑制核因子κ-轻链增强剂的活化B细胞活化在小鼠CLP模型。因此，骨髓间充质干细胞有可能成为治疗脓毒症所致急性肺损伤的新药物。(C)2020年，任作家。爱思唯尔公司出版
Background: Acute lung injury is a common complication of sepsis in intensive care unit patients. Inflammation is among the main mechanisms of sepsis. Therefore, suppression of inflammation is an important mechanism for sepsis treatment. Mesenchymal stem cells (MSCs) have been reported to exhibit antimicrobial properties.Objective: The present study investigated the effects of MSCs on sepsis-induced acute lung injury.Methods: Male C57BL/6 mice underwent a cecal ligation and puncture (CLP) operation to induce sepsis and then received either normal saline or MSCs (1 x 10(6) cells intravenously) at 3 hours after surgery. Survival after surgery was assessed. Lung injury was assessed by histology score, the presence of lung edema, vascular permeability, inflammatory cell infiltration, and cytokine levels in bronchoalveolar lavage fluid. Finally, we tested nuclear factor kappa-light-chain-enhancer of activated B cells activation in lung tissue.Results: As expected, CLP caused lung injury as indicated by significant increases in the histopathology score, lung wet to dry weight ratio, and total protein concentration. However, mice treated with MSCs had amelioration of the lung histopathologic changes, lung wet to dry weight ratio, and total protein concentration. The levels of cytokines tumor necrosis factor alpha, interleukin 6, interleukin 1 beta, and interleukin 17 in bronchoalveolar lavage fluid were dramatically decreased after MSCs treatment. In contrast, expression of interleukin 10 was increased after MSCs treatment. Moreover, mice treated with MSCs had a higher survival rate than the CLP group. Neutrophil infiltration into bronchoalveolar lavage fluid was attenuated after MSCs injection, but the amounts of macrophages observed in the MSC group showed no significant differences compared with the CLP group. In addition, MSCs treatment significantly reduced nuclear factor kappa-light-chain-enhancer of activated B cells activation in lung tissue.Conclusions: Based on the above findings, treatment with MSCs dampened the inflammatory response and inhibited nuclear factor kappa-light-chain-enhancer of activated B cells activation in the mouse CLP model. Thus, MSCs may be a potential new agent for the treatment of sepsis-induced acute lung injury. (C) 2020 The Authors. Published by Elsevier Inc.