中文摘要：

目的 探讨骨髓间充质干细胞（BMSC）调节多器官功能障碍综合征（MODS）炎症反应的潜在机制,特别是相关炎性因子的表达,为临床治疗MODS提供新的理论及实验依据.方法 提取并培养4周龄雌性SD大鼠BMSC,以第4代BMSC用于实验.按照随机数字表法将60只雌性SD大鼠分成假手术（Sham）组、MODS组和BMSC组,每组20只.经股静脉注射脂多糖（LPS）1 mg/kg复制大鼠MODS模型;Sham组注射等量磷酸盐缓冲液（PBS）;BMSC组于制模后2 h经尾静脉输注BMSC（1×10^6/只）0.5 mL.观察各组大鼠72 h存活情况;术后72 h取腹主动脉血行血常规和生化检查;应用蛋白芯片检测34种相关炎性因子,以信号比值〉2.0或者〈0.5为差异表达因子,用酶联免疫吸附试验（ELISA）验证有明显变化的炎性因子表达;留取心、肾、小肠组织,苏木素-伊红（HE）染色后观察病理学改变.结果 Sham组、MODS组和BMSC组术后72 h分别存活20、12、16只大鼠.与Sham组比较,MODS组血常规、肝肾功能及心肌酶指标出现明显异常,心、肾、小肠组织明显损伤;经BMSC治疗后各器官功能明显改善,组织损伤减轻.细胞因子芯片分析显示,34个目标因子中白细胞介素-4（IL-4）和晚期糖基化终末产物受体（RAGE）为差异表达细胞因子,MODS/Sham组、BMSC/Sham组、BMSC/MODS组IL-4信号比值分别为0.397、1.124、2.826,RAGE信号比值分别为6.197、1.552、0.250.ELISA验证结果也显示,与Sham组比较,MODS组IL-4明显下降（ng/L：3.59±1.21比29.10±5.78）,RAGE明显升高（ng/L：1.09±0.04比0.11±0.03,均P〈0.01）;与MODS组比较,BMSC组IL-4明显升高（ng/L：9.59±2.21比3.59±1.21,P〈0.01）,RAGE明显降低（ng/L：0.29±0.07比1.09±0.04,P〈0.05）.结论 BMSC移植治疗可以调节MODS大鼠炎性因子IL-4及RAGE的表达,促进组织器官功能修复,从而提高存活率;BMSC有望作为炎症性疾病细胞疗法的种子细胞.

英文摘要：

Objective To investigate the underlying mechanism of bone marrow mesenchymal stem cells （BMSC） modulating the inflammatory response during the multiple organ dysfunction syndrome （MODS）, especially the expression of inflammatory cytokines, which will provide new theoretical and experimental basis of MODS in clinic. Methods BMSC of Sprague-Dawley （SD） rat （female, 4 weeks） was extracted and cultivated, and the 4th passage were used in experimental study. According to the random number table, 60 female SD rats were divided into three groups （n = 20 per group）： sham group, MODS group, BMSC group. MODS model in rats was induced by lipopolysaccaride （LPS, 1 mg/kg） via femoral vein injection. Sham group was injected with the sterile phosphate buffer saline （PBS） in the same volume. BMSC group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation （1×10^6/cells） through the tail vein. The survival rate was observed after 72 hours in each group. Abdominal aortic blood was collected for routine blood and biochemical examination at 72 hours after operation. Protein microarray was used to detect the related 34 inflammatory cytokines. Signal ratio was defined as the differentially expressed factors when it was more than 2.0 or less than 0.5. And enzyme linked immunosorbent assay （ELISA） was be applied to validate the significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue was harvested, then their pathological changes were observed by hematoxylin eosin （HE） staining.Results 20, 12, 16 rats lived in sham group, MODS group and BMSC group respectively at 72 hours after operation. Compared with the sham group, the indicators （routine blood, liver and kidney function, myocardial enzyme） were apparently unusual, and the heart, kidney, intestine tissue were injured obviously in the MODS group. After BMSC administration, the organ function was improved and tissue damaged was alleviated significantly. Protein microarray showed that interleukin