人脐带间充质干细胞移植对脓毒症小鼠的保护作用研究  

Therapeutic Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Septic Mice

作　　者：宋昱庆[1] 朱明[1] 何骁[1] 郭韡[1] 邢伟[1] 梁东兰 安天琛 敖罗权 黄宏[1] 蒋东坡[2] 徐祥[1] 

机构地区：[1]第三军医大学第三附属医院野战外科研究所,创伤、烧伤与复合伤国家重点实验室,重庆400042 [2]第三军医大学第三附属医院野战外科研究所重症监护室,重庆400042

出　　处：《中国细胞生物学学报》2017年第8期1000-1007,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81372027);重庆市基础与前沿研究计划院士专项(批准号:csts2014jcyjys10002)资助的课题~~

摘　　要：为了评价人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,h UCMSCs)移植对脓毒症小鼠的疗效,作者将90只小鼠随机均分为3组:假手术(Sham)组、PBS治疗组和h UC-MSCs治疗组。治疗组小鼠采用盲肠结扎穿孔(cecal ligation and puncture,CLP)方式建立脓毒症模型;假手术组小鼠仅开腹探查盲肠,不行CLP。Sham组和PBS治疗组术后3h经尾静脉注射0.2mL PBS,hUC-MSCs治疗组注射等体积的h UC-MSCs悬液(含细胞7.5×10~5/mL)。术后24 h,流式细胞术检测各组小鼠外周血及腹腔灌洗液(peritoneal lavage fl uid,PLF)中的中性粒细胞数量,ELISA检测血清炎症因子水平,生化检验评价肝肾功,HE(hematoxylin and eosin)染色评估肝、肾、肺组织病理变化。观察术后小鼠一般情况,绘制120 h生存曲线。结果显示,hUC-MSCs可以显著改善脓毒症小鼠一般状况,减少中性粒细胞浸润,降低小鼠体内炎症水平,改善器官功能,减轻组织器官损伤,显著提高小鼠存活率。该研究显示了人脐带间充质干细胞移植对脓毒症小鼠的良好保护作用。The aim of this study was to evaluate the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells（h UC-MSCs） in septic mice. A total of 90 C57BL/6 mice with cecal ligation and puncture（CLP）-induced sepsis were randomly divided into 3 groups, i.e. PBS treating group（CLP＋PBS）, h UC-MSCs treating group（CLP＋h UC-MSCs）, and Sham group treated with sham surgery, then PBS（Sham＋PBS）. PBS and h UC-MSCs suspension（7.5×105 cells/m L） were administered via tail vein injection in a volume of 0.2 m L per mouse at 3 h after CLP or sham surgery. All mice received subcutaneous injection of antibiotics at 6 h and 18 h after surgery. At 24 h after surgery, the abundance of neutrophils in peripheral blood and in peritoneal lavage fl uid, serum infl ammatory cytokines, and serum markers of liver and kidney function were analyzed by fl ow cytometry, ELISA, and biochemical tests, respectively. Meanwhile, the pathological changes in liver, kidney and lung were assessed by the HE（hematoxylin and eosin） staining. The survival rates of mice in each group were evaluated every 12 h till 120 h, and then the survival curves were plotted. The mouse model of sepsis in this study was reproducible. When compared to PBS-treated mice, h UC-MSCs-treated mice showed a significant decrease in the ratios of serum pro-inflammatory cytokines（TNF-α, IL-1β and IL-6） to an anti-inflammatory cytokine（IL-10） and an obvious improvement in survival and general status. And, it could reduce polymorphonuclear neutrophils infiltration. The levels of serum markers of liver and kidney function（ALT, AST, Crea and Urea） and the pathologic lesion of organs（liver, kidney and lung） were significantly lower in h UC-MSC-treated mice than that in PBS-treated mice. Xenotransplantation of h UC-MSCs into CLP-induced septic mice showed an obvious protective effect.

关 键 词：人脐带间充质干细胞 脓毒症 炎症 保护作用 

分 类 号：R459.7[医药卫生—急诊医学]