骨髓间充质干细胞治疗重症急性胰腺炎实验研究

摘要

Objective To investigate the mechanism of acute inflammatory response and tissue repair when rats accepted transplanted bone marrow mesenchymal stem cells (MSC) in severe acute pancreatitis (SAP).Methods A total of 40 rats were randomly divided into 4 groups which included the normal group (n=10),the model severe acute pancreatitis group (n=10),the transplanted bone marrow mesenchymal stem cells group (n =10),and the combination of bone marrow mesenchymal stem cells and granulocyte colony-stimulating factor (G-CSF) group (n=10).To cure the acute severe pancreatic injury caused by SAP,rats were injected with EDU-labeled MSCs and granulocyte colonystimulating factor (Gr-CSF).The conversion rate of MSCs to pancreatic cells or MSCs to endothelial cells was detected to assess the role of MSCs in tissue regeneration and repair.The expression of amylase,interleukin-6 (IL-6),and interleukin-10 (IL-10) in serum was detected to assess the role of MSCs in an acute inflammatory response.Results The concentrations of amylase and IL-6 were reduced and the concentration of IL-10 was increased in MSC and MSC+G-CSF groups after the onset of SAP.Flow cytometry showed a small amount of MSCs converting to endothelial or pancreatic cells,but the conversion rate was relatively low.Conclusions MSCs can play an important role in the antipre-release of inflammatory mediators,reducing acute immune response to control the acute inflammatory response in SAP.Moreover,MSCs can repair a damaged pancreas by converting into both pancreatic and endothelial cells.%目的 研究骨髓间充质干细胞(mesenchymal stem cells,MSC)移植对重症急性胰腺炎(severe acute pancreatitis,SAP)急性炎症反应的调控及组织修复的机制.方法 将40只大鼠随机分为正常组、SAP模型组、MSC移植组、MSC+粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)联合组.SAP大鼠注射EDU标记的MSC和G-CSF治疗SAP引起的急性重度胰腺损伤.通过检测MSC向内皮细胞、胰腺细胞分化的转化率,研究MSC对胰腺损伤的再生和修复作用；通过检测血清白细胞介素(IL)中的IL-6、IL-10的浓度以及淀粉酶的含量,研究MSC对SAP炎症介质的影响及急性炎症反应的调控机制.结果 MSC、MSC+ G-CSF组相对于SAP组血清淀粉酶浓度有不同程度的降低,炎性介质IL-6的变化趋势与血清淀粉酶一致,而细胞因子合成抑制因子IL10含量逐渐升高.流式结果显示有少量MSC转化为内皮细胞和胰腺细胞.结论 MSC不但能通过其在抗炎症介质释放、减轻急性免疫反应等方面的重要功能达到控制SAP急性炎症反应的作用,而且MSC还可通过分化为胰腺细胞和内皮细胞修复受损胰腺.