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The role of HMGB1 in BMSC transplantation for treating MODS in rats

机译:HMGB1在BMSC移植治疗大鼠MOD的作用

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摘要

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-kappa B 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-kappa B signal pathway. It suggests that HMGB1 is an attractive potential target for the development of new therapeutic strategies for MODS.
机译:骨髓间充质干细胞(BMSCs)治疗多器官功能障碍综合征(MODS)的影响仍然未知,机制尚不清楚。因此,本研究的目的是研究细胞内高迁移率组箱1蛋白(HMGB1)对MODS治疗BMSC的影响。通过下肢浅表静态静脉,然后随机分配给四组:Sham组,Mods Plus BMSC组,Mods加乙基丙酮酸(EP)组(EP)组,随机分配给1mg / kg脂多糖(LPS)。 Mods Plus BMSCS加上EP组。二十四小时后,处死基团的大鼠,然后收集血液和组织以评估组织组织病理学,细胞凋亡,炎症水平和器官功能的变化。通过RT-QPCR和Western印迹监测HGMB1表达。还评估了蛋白质水平的RAGE / TLR2 / TLR4和NF-Kappa B的表达。通过改善细胞凋亡,炎症反应和器官功能障碍,对损伤部位没有影响,BMSCs和/或EP对LPS诱导的组织病理学损伤表现出突出的保护作用。此外,BMSCs和/或EP抑制蛋白质水平在蛋白质水平的HMGB1,RAGE,TLR2和TLR4表达的LPS诱导的上调,并在MOD的大鼠模型中损害P65磷酸化。这些发现表明HMGB1通过调节TLR2,介导的NF-Kappa B信号途径来参与MODS的BMSC处理。它表明HMGB1是开发Mods新治疗策略的有吸引力的潜在目标。

著录项

  • 来源
    《Cell and Tissue Research》 |2018年第2期|共12页
  • 作者单位

    Second Peoples Hosp Yunnan Prov Dept ICU 176 Qingnian Rd Kunming 650021 Yunnan Peoples R China;

    Second Peoples Hosp Yunnan Prov Dept ICU 176 Qingnian Rd Kunming 650021 Yunnan Peoples R China;

    First Peoples Hosp Yunnan Prov Dept Obstet Kunming Yunnan Peoples R China;

    First Peoples Hosp Yunnan Prov Dept Anesthesiol Kunming Yunnan Peoples R China;

    Binzhou Med Univ Affiliated Hosp Dept Anesthesiol Binzhou Peoples R China;

    Second Peoples Hosp Yunnan Prov Dept ICU 176 Qingnian Rd Kunming 650021 Yunnan Peoples R China;

    Second Peoples Hosp Yunnan Prov Dept ICU 176 Qingnian Rd Kunming 650021 Yunnan Peoples R China;

    Kunming Gen Hosp Stem Cell Engn Lab Yunnan Prov Chengdu Mil Command Kunming Yunnan Peoples R;

    Chinese Acad Sci Kunming Inst Zool Kunming Biol Divers Reg Ctr Instruments Kunming Yunnan;

    Second Peoples Hosp Yunnan Prov Dept ICU 176 Qingnian Rd Kunming 650021 Yunnan Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    MODS; BMSC; HMGB1; Lipopolysaccharide; NF-kappa B signal pathway;

    机译:MODS;BMSC;HMGB1;脂多糖;NF-KAPPA B信号途径;

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