骨髓间充质干细胞治疗重症急性胰腺炎实验研究

Research on bone marrow mesenchymal stem cells in the treatment of severe acute pancreatitis

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IL-10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。

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 mesenchymai 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 colony stimulating factor （G 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 am ylase, 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 inflamma tory response in SAP. Moreover, MSCs can repair a damaged pancreas by converting into both pancreatic and endothelial cells.