与大鼠胰岛细胞联合移植的骨髓间充质干细胞的免疫调节作用  

Immune regulation of different genotypes of bone marrow mesenchymal stem cells on allogenic islet transplantation

作　　者：林雨佳[1] 高峰[1] 吴德全[1] 

机构地区：[1]哈尔滨医科大学附属第二医院,150080

出　　处：《中华器官移植杂志》2011年第3期172-176,共5页Chinese Journal of Organ Transplantation

基　　金：中国博士后科学基金（20080440910）;黑龙江省卫生厅科研课题（2009-149）

摘　　要：目的研究同种异体或自体的大鼠骨髓间充质干细胞（MSC）与胰岛肝内联合移植对胰岛移植物的免疫调节作用及其机制。方法以链佐星制备Lewis大鼠的糖尿病模型，作为胰岛移植受者，分为3组：单纯移植组大鼠经门静脉单独移植SD大鼠胰岛6000 IEQ／kg；同系MSC组大鼠经门静脉共同移植1×10^9／L的Lewis大鼠MSC 1ml与SD大鼠胰岛6000 IEQ／kg；同种MSC组大鼠经门静脉共同移植1×10^9／L的SD大鼠MSC 1ml与SD大鼠胰岛6000IEQ／kg。检测受鼠的血糖变化，术后1、3d大鼠外周血γ干扰素（IFN-γ）、白细胞介素（IL）-2、IL-4和IL-10的含量。结果3组大鼠术后第1天血糖均下降到13．9mmol／L以下。同系MSC组移植物存活时间为（11．38±4．03）d，同种MSC组为（5．50±2，07）d，单纯移植组为（2．88±1．25）d（P〈0．01）。术后1、3d，单纯移植组IFN-γ和IL-2的含量显著高于同系MSC组和同种MSC组（P〈0．01），同种MSC组IFN-γ和IL-2的含量高于同系MSC组（P〈0．05）；单纯移植组IL-10的含量低于同系MSC组和同种MSC组（P〈0．01），同系MSC组IL-10的含量与同种MSC组相比较，差异无统计学意义（P〉0．05）；各组IL-4含量的差异无统计学意义（P〉0．05）。结论MSC与同种胰岛共移植可以延长胰岛移植物存活时间，应用同系MSC的效果优于同种异体MSC。共移植的MSC主要通过减少TH1类细胞因子（IFN-7和IL-2）的表达使受者TH1／TH2平衡向TH2方向偏移。Objective To compare the immune regulation of syngenic and allogenic mesenchymal stem cells （MSCs） in the transplantation combined with islets. Methods After induction of diabetes in 30 Lewis rats with streptozotocin （STZ）, the recipient Lewis rats received islets from SD rats combined with syngenic （group B） or allogenic （group C） MSCs injection via the portal vein. The group of islets transplanted alone served as control （group A）. The survival time of grafts in all groups was assessed by the level of blood glucose. ELISA was used to detect the levels of interferon-γ（IFN-γ）, interleukin 2 （IL-2）, IL-4 and IL-10 in the peripheral blood on the 1st and 3rd day after transplantation. Results The blood glucose levels in all three groups were decreased in a normal range （13. 9 mmol/L） and the survival time of grafts in group B （11.38 ± 4. 03 days） was significantly longer than in group C （5.50 ± 2. 07 days） as well as group A （2. 88± 1.25 dayS）. On the 1st and 3rd day after transplantation, the levels of TH 1 cytokines IFN-γ and IL-2 in group A were significantly higher than in groups C and B （P〈0. 05）. Meanwhile the levels of TH2 cytokine IL-10 were increased in group B, but there was no significant difference between groups A and C （P〈 0. 05）. The levels of IL-4 had no significant difference among these three groups （P 〈 0. 05）. Conclusion Islet transplantation combined with MSCs could prolong the survival time of grafts. Syngenic MSCs, superior to allogenic ones, were more effective in changing the balance of TH 1/TH2 to TH2. Decreased expression of TH 1 cytokine （IFN-γ, IL-2）, which was closely related to the induction of immune tolerance, was beneficial to the long-term survival of grafts.

关 键 词：胰岛移植 间质干细胞 T淋巴细胞 辅助诱导 免疫耐受 糖尿病 

分 类 号：R657.5[医药卫生—外科学]