Department of ICU, The Second People's Hospital of Yunnan Province, 176 Qingnian Road, Wuhua District, Kunming, 650021, China.
Department of Obstetrics, The First People's Hospital of Yunnan Province, Kunming, China.
Cell Tissue Res. 2018 Aug;373(2):395-406. doi: 10.1007/s00441-018-2823-0. Epub 2018 Apr 10.
The effect of bone marrow mesenchymal stem cells (BMSCs) in treatment for multiple organ dysfunction syndrome (MODS) remains unknown and the mechanism is still unclear. Therefore, the goal of this study is to investigate the effects of intracellular high mobility group box 1 protein (HMGB1) on BMSCs treating for MODS. The rats were given 15% blood loss plus 1 mg/kg lipopolysaccharide (LPS) via lower extremity superficial venous, then randomly allocated into four groups: sham group, MODS group, MODS plus BMSC group, MODS plus ethyl pyruvate (EP) group, MODS plus BMSCs plus EP group. Twenty-four hours later, rats in groups were sacrificed and then the blood and tissues were collected to evaluate the changes of tissue histopathology, cell apoptosis, inflammation level and organ function. The HGMB1 expression was monitored by RT-qPCR and Western blot. The expression of RAGE/TLR2/TLR4 and NF-κB at the protein levels was also assessed. BMSCs and/or EP exhibits an outstanding protective effect against LPS-induced histopathological injury by improving cell apoptosis, inflammatory response and the organ dysfunction but no effect on BMSC homing to the injury site. Moreover, BMSCs and/or EP inhibited LPS-induced upregulation of HMGB1, RAGE, TLR2 and TLR4 expression at protein levels and compromised p65 phosphorylation in the rat model of MODS. These findings suggest that HMGB1 is involved in BMSC treatment for MODS, through regulation of the TLR2, TLR4-mediated NF-κB signal pathway. It suggests that HMGB1 is an attractive potential target for the development of new therapeutic strategies for MODS.
骨髓间充质干细胞（BMSCs）治疗多器官功能障碍综合征（MODS）的效果尚不清楚，其机制仍不清楚。因此，本研究旨在探讨细胞内高迁移率族蛋白 B1（HMGB1）对 BMSCs 治疗 MODS 的影响。大鼠通过下肢浅静脉给予 15%失血加 1mg/kg 脂多糖（LPS），然后随机分为四组：假手术组、MODS 组、MODS+BMSC 组、MODS+乙基丙酮酸（EP）组、MODS+BMSC+EP 组。24 小时后，处死各组大鼠，采集血液和组织，评估组织病理变化、细胞凋亡、炎症水平和器官功能的变化。通过 RT-qPCR 和 Western blot 监测 HGMB1 表达。还评估了 RAGE/TLR2/TLR4 和 NF-κB 在蛋白质水平的表达。BMSC 和/或 EP 通过改善细胞凋亡、炎症反应和器官功能，对 LPS 诱导的组织病理损伤表现出显著的保护作用，但对 BMSC 向损伤部位归巢没有影响。此外，BMSC 和/或 EP 抑制 LPS 诱导的 HMGB1、RAGE、TLR2 和 TLR4 蛋白表达上调，并削弱了 MODS 大鼠模型中 p65 磷酸化。这些发现表明，HMGB1 参与了 BMSC 治疗 MODS，通过调节 TLR2、TLR4 介导的 NF-κB 信号通路。这表明 HMGB1 是开发 MODS 新治疗策略的有吸引力的潜在靶点。
