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不同浓度间充质干细胞治疗对脂多糖诱导的急性呼吸窘迫综合征大鼠模型的影响。

Effects of different concentrations of mesenchymal stem cells treatment on LPS-induced acute respiratory distress syndrome rat model.

机构信息

Stem Cell Biology and Regenerative Medicine Institution, Beijing Yi-Chuang Institute of Bio-Industry, Beijing, China.

State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China.

出版信息

Exp Lung Res. 2021 May-Jun;47(5):226-238. doi: 10.1080/01902148.2021.1897191. Epub 2021 Mar 22.

Abstract

This study was prospectively designed to investigate the effects of different concentrations of mesenchymal stem cells treatment on respiratory mechanics, oxygenation, hemodynamics and inflammatory response in LPS-induced acute respiratory distress syndrome (ARDS) rat model. : One hundred and twenty six LPS-induced ARDS model rats (weighted 200-220 g) were randomly divided into three groups: 1) Control group (N = 42); 2) low-dose hUC-MSC treatment group (MSC group 1, 1x10 cell/kg, N = 42); 3) high-dose hUC-MSC treatment group (MSC group 2, 2x10 cell/kg, N = 42), sham operation group as healthy group (N = 15). The rats were observed closely for 24 hours after hUC-MSC treatment, and the survival rate was calculated. At 24 hours, all rats were tested for hemodynamics, blood gas analysis, heart, lung, liver and kidney functions, inflammatory factors detection in blood samples and broncho-alveolar lavage fluid (BALF). The lung tissue of the rats was collected for HE staining analysis. : After LPS injection, ARDS was obvious in all LPS-infused rat groups, consistent with severe acute lung injury and high death rate. However, compared with the control group, a single intravenous injection hUC-MSC at dose of 1 × 10 cells/kg (low dose group) and 2 × 10 cells/kg (high dose group) reduced the mortality of rats with LPS-induced ARDS, as well as improving the lung function, increased the arterial oxygen pressure, improved the heart function, and reduced the levels of inflammatory factors including IL-1β, IL-6, and TNF-α. In addition, the high dose MSC group showed better lung injury therapeutic effects than the low dose MSC group. Data from this study demonstrated that injection of hUC-MSC had a significant therapeutic effect in treating the rat model of LPS-induced ARDS and multiple organ function injury.

摘要

这项研究旨在前瞻性地研究不同浓度间充质干细胞(MSC)治疗对脂多糖(LPS)诱导的急性呼吸窘迫综合征(ARDS)大鼠模型呼吸力学、氧合、血液动力学和炎症反应的影响。

126 只 LPS 诱导的 ARDS 模型大鼠(体重 200-220g)随机分为三组:1)对照组(N=42);2)低剂量 hUC-MSC 治疗组(MSC 组 1,1x10 细胞/kg,N=42);3)高剂量 hUC-MSC 治疗组(MSC 组 2,2x10 细胞/kg,N=42),假手术组作为健康组(N=15)。hUC-MSC 治疗后密切观察大鼠 24 小时,计算存活率。24 小时时,所有大鼠均进行血液动力学、血气分析、心、肺、肝、肾功能检测,检测血样和支气管肺泡灌洗液(BALF)中的炎症因子,并收集大鼠肺组织进行 HE 染色分析。

LPS 注射后,所有 LPS 输注大鼠组均出现明显的 ARDS,与严重急性肺损伤和高死亡率一致。然而,与对照组相比,单次静脉注射 1x10 细胞/kg(低剂量组)和 2x10 细胞/kg(高剂量组)的 hUC-MSC 可降低 LPS 诱导的 ARDS 大鼠的死亡率,改善肺功能,增加动脉血氧分压,改善心功能,并降低包括 IL-1β、IL-6 和 TNF-α在内的炎症因子水平。此外,高剂量 MSC 组的肺损伤治疗效果优于低剂量 MSC 组。

这项研究的数据表明,hUC-MSC 注射对治疗 LPS 诱导的 ARDS 和多器官功能损伤大鼠模型具有显著的治疗效果。

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