1,25(OH)_2D_3对糖尿病大鼠胰腺移植后急性排斥反应的免疫调控研究  

Study of immunoregulation of 1,25(OH)_2D_3 in prevention of acute rejection of pancreas transplantation in diabetic rats

作　　者：张轩[1] 徐泽宽[1] 韩曙光[1] 于刚[1] 曹晓飞[1] 苗毅[1] 

机构地区：[1]南京医科大学第一附属医院胆胰外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2008年第2期244-248,264,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省卫生厅135重点人才基金资助项目(135-56)

摘　　要：目的:探讨1,25(OH)_2D_3对大鼠胰腺移植急性排斥反应的免疫调控作用。方法:以F344大鼠为供体,Lewis大鼠为受体,分A组(急性排斥对照组);B组(雷帕霉素治疗组);C组[1,25(OH)_2D_3治疗组],每组15例;观察术后各组血糖变化,移植物存活以及组织病理学改变;流式细胞检测受体血、脾以及移植物CD4+T细胞、CD8+T细胞、CD4+CD25+T细胞表达水平;ELISA检测受体血清IL-2、4、10、12表达水平;在诱导Lewis大鼠骨髓细胞定向分化为树突状细胞(DC)时加入1,25(OH)_2D_3,流式细胞仪检测CD80,CD86及MHCⅡ类分子表达情况。结果:预防性使用1,25(OH)_2D_3、保护移植物功能(血糖5.12±0.89VS12.41±1.16),延长移植后受体平均存活时间;CD8+T细胞计数C、B与A组相比均有减少,差异有统计学意义(P<0.01)。CD4+T细胞C、B与A组的差异有统计学意义。CD4+CD25+调节性T细胞A、B、C组逐渐升高,有统计学意义(P<0.01),且以C组较为明显(C组VSA组P<0.01);血清Th1类细胞因子浓度明显降低,Th2类细胞因子浓度明显增高;在体外实验中,1,25(OH)_2D_3显著抑制了DC的成熟过程及其表面共刺激分子的表达。结论:1,25(OH)_2D_3可抑制DC发育成熟,诱导产生基因耐受性树突细胞,促进调节性T淋巴细胞的增生,抑制致病性T淋巴细胞,抑制急性排斥反应,延长受体存活时间。Objective：To investigate the effect of 1,25（OH）2D3 on prevention of acute rejection model of F344-Lewis rat pancreas transplantation. Methods：Pancreatic allograft from F344 rats was transplanted to Lewis recipients. Group A （untreated allogeneic control ） , Group B （rapamycin treatment）,Group C （1,25 （OH）2D3 treatment）, 15 rats were in each.;The blood glucose in the recipients, the pathological changes of the allografts and the survival of pancreatic allografts were observed. And the recipients＇ peripheral blood,spleens and grafts were harvested from recipient to determine the CD3^＋ CD8^＋ T cells,CD4^＋ T cells and CD4^＋CD25^＋ T by flow cytometry. After transplantation,the level of serum interferon-2,4, 10, 12 in the recipients was determined by ELISA kit analysis also. Dendritic Cells （DC） of Lewis were derived from bone marrow cells in the culture with 1,25 （OH）2D3. The expression of C D80, CD86 and MHC Ⅱ molecules was assessed by flow cytometry. Results： 1,25 （OH）2D3 significantly inhibited acute rejection,protected allografted function [blood glucose （5.12 ± 0.89） VS （12.41 ± 1.16）], and prolonged recipient survival. The population of CD8^＋T cell and CD4^＋T cell decreased in group B and C,though more CD4^＋CD25^＋ T cells were detected in group C. The differences in group C were apparent compared to A and B （P 〈 0.01）. Concentration of Thl-type cytokine in serum decreased markedly,and Th2-type cytokine increased significantly. The mature of DCs was inhibited by 1,25 （OH）2D3, and CD80, CD86, MHC Ⅱ molecules expression on the DC was significantly decreased in the presence of 1,25 （OH）2D3. Conclusion：1,25 （OH）2D3 could not only induce tolerogenic DCs but also might be enhance the number of CD4^＋CD25^＋ regulatory T cells. In such a way,the acute rejection might be inhibited, and the recipients survival might be prolonged.

关 键 词：1 25(OH)2D3 胰腺移植 急性排斥 树突状细胞 

分 类 号：R392.4[医药卫生—免疫学]