肌源性干细胞移植修复糖尿病胰岛功能的旁分泌机制研究

Paraerine mehcanism of MDSCs Promote Panereatie islets of diabetic mice

目的阐明肌源性干细胞移植修复糖尿病小鼠胰岛功能的旁分泌机制及参与胰岛修复的信号通路。方法取6只大鼠的前肢肱三头肌与后肢腓肠肌,采用差速贴壁法纯化扩增大鼠肌源性干细胞,传至第4代用于移植。取40只大鼠,通过尾静脉注射链脲佐菌素建立糖尿病模型,32只成功造模,取24只随机均分为3组:实验a组胰腺被膜下移植肌源性干细胞约2×106个,实验b组胰腺被膜下移植(LY294002(10umol/L)+MD-SCs2×106),模型对照组同法给予等量不含细胞的培养液。余8只大鼠作为正常对照组。结果血糖变化:移植后1周,实验a组血糖出现显著下降并一直持续下降至第4周,与模型对照组比较差异有统计学意义。胰岛细胞和胰岛β细胞数变化:移植后4周模型对照组胰岛数目仍较少,胰岛β细胞也较少,实验a组小鼠胰岛数目增加,胰岛β细胞数目也增加,与模型对照组比较差异有显著统计学意义。Western Blotting检测发现实验a组pAKT表达显著上调,加入LY294002后即使加入MDSCs后也不能上调pAKT。结论肌源性干细胞移植在糖尿病大鼠胰腺被膜下对胰岛功能有修复作用。

【Objective】 To investigatet heparacrine mechanisms and the role of signaling pathway of MDSCS promote Panereatic islets of diabetic mice.【Methods】 Triceps brachii of the forelimbs and gastrocnemius of the postlimbs of 6 rats were obtained.MDSCs were purified and amplified using the differential adherence method.Forty rat models of diabetes were established by infusing streptozotolin via the tail vein.Thirty-two successful rat models were obtain,and twenty-four of them were randomly divided into three groups.Experiment a group was pancreatic capsuleinjected with 2×106MDSCs.Experiment b group was pancreatic capsule injected with2×106MDSCs and LY29002 10umol/L.The model control group was injected with the same volume of cell medium Remaining eight rats served as the normal control group.【Results】 Blood glucose ：bloodglucose levels of experiment a group were significantly reduced at one week after transplantation and sustained to reduce at four weeks after transplantation vs blood glucose of experiment b group p0.05.Four weeks after transplantation,the number of experiment a group was large than control mice.Four weeks after transplantation,the beta cell number of experiment a group was larger than experiment b group.Western Blotting detected：pAKT expressed in islets of experiment a group were higher than experiment b group.【Conclusion】 Transplantation DMSCs in pancreatic capsule repair islets of diabetic mice by paracrine mechamism.