Experimental study of umbilical mesenchymal stem cells transplantation with over expression of chemokine receptor 4 in treatment of rats with acute liver failure
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摘要: 目的 探讨高表达趋化因子受体4(CXCR4)的脐带间充质干细胞(UMSCs)移植治疗D-氨基半乳糖/脂多糖(D-GalN/LPS)所致急性肝衰竭大鼠的疗效。 方法 采用胶原酶和胰酶两步法分离大鼠UMSCs, 采用肝衰竭大鼠血清诱导大鼠脐带间充质干细胞高表达CXCR4。以D-GalN/LPS腹腔注射建立急性肝衰竭大鼠模型,并于造模后24、48、96、144 h经大鼠尾部静脉分别注入UMSCs(移植对照组)、高表达CXCR4的UMSCs(移植治疗组)、等量无菌磷酸盐缓冲溶液(PBS)溶液(空白对照组)。移植后第3、7天收集血液标本,第7天留取肝脏和肺脏组织标本,观察各组大鼠7 d生存率、肝功能和肝肺组织病理学变化。 结果 移植治疗组、移植对照组的7 d生存率分别为66.7%、53.3%, 均显著高于空白对照组的20.0%(P<0.05)。移植治疗组肝功能及肝脏炎症损伤均较移植对照组和空白对照显著改善(P<0.05), 且未见肺栓塞等不良反应。 结论 UMSCs移植对D-GalN/LPS所致的急性肝衰竭大鼠具有显著的治疗效果,而高表达CXCR4的UMSCs效果更佳。Abstract: Objective To explore the therapeutic effect of umbilical mesenchymal stem cells transplantation(UMSCs)with over expression of chemokine receptor 4(CXCR4)in treatment of rats with acute liver failure induced by D-galactosamine and lipopolysaccharide(D-GalN/LPS). Methods The UMSCs of rats were separated by two-step method of collagenase and trypsin, and over expression of CXCR4 in UMSCs of rats were induced by serum of rats with acute liver failure. D-GalN/LPS was injected intraperitoneally to establish model of rats with acute liver failure. UMSCs(transplanted control group), UMSCs with high expression of CXCR4(transplanted treatment group)and equal amount of sterile phosphate buffer saline(PBS)solution(blank control group)were injected into the tail vein of rats at 24, 48, 96 and 144 hours after modeling. Blood samples were collected on the 3rd and 7th days after transplantation. Liver and lung tissue samples were collected on the 7th day after transplantation. The 7-day survival rate, liver function, and pathological change of liver and lung were observed. Results The 7-day survival rate in the transplanted treatment group and the transplanted control group was 66.7% and 53.3% respectively, which was significantly higher than 20.0% - in the blank control group(P<0.05). The improvement of liver function and the liver inflammatory injury in the transplanted treatment group was significantly better than those in the transplanted control group and the blank control group(P<0.05), and no adverse reactions such as pulmonary embolism were observed. Conclusion UMSCs transplantation therapy has a significant effect in treatment of rats with acute liver failure induced by D-GalN/LPS, and UMSCs with high expression of CXCR4 has better effect.
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