1α,25二羟维生素D_3对1型糖尿病Th1/Th2平衡的调节作用  

Immunomodulatory effects of lα,25-dihydroxyvitamin D_3 on the balance of Th1/Th2 in T1DM

作　　者：张翼[1] 张松[1] 王建平[1] 向斌[1] 周海峰[1] 杨治芳[1] 何伟民[2] 周智广[1] 

机构地区：[1]中南大学糖尿病中心湘雅二医院代谢内分泌研究所,长沙410011 [2]福建医科大学附属泉州市第一医院内分泌科

出　　处：《中国糖尿病杂志》2007年第9期515-518,共4页Chinese Journal of Diabetes

基　　金：教育部"跨世纪优秀人才培养计划"基金资助项目(2002-48);国家自然科学基金资助项目(30400217);福建省泉州市科技重点项目(2007229)

摘　　要：目的探讨1α,25二羟维生素D3_1,25D3)对经典1型糖尿病(T1DM)Th1/Th2比值平衡的免疫调节作用。方法选择6例新发病、GAD-Ab阳性的T1DM患者,6名年龄、性别匹配的健康志愿者为对照(NC);间接免疫荧光鉴定细胞维生素D受体(VDR)的表达;免疫印迹法分析VDR蛋白的表达;连续梯度离心法分离人外周单个核细胞(PBMC);酶联免疫斑点法定量检测GAD65反应性分泌IFN-γ、IL-4细胞,分别代表Th1、Th2细胞。结果(1)T1DM的PBMC胞核表达VDR;(2)T1DM组Th1、Th2、Th1/Th2均值分别为18.0、3.0、6.0,NC组为2.5、3.5、0.71,T1DM组1,25D3作用后则分别为5.6、4.5、1.22,溶剂(无水乙醇)对照组分别为1.5、3.2、4.8。T1DM组的Th1及Th1/Th2均明显高于NC组(P<0.01);与溶剂组比较,T1DM组1,25D3作用后的Th1及Th1/Th2均明显降低(P<0.05);三组间的Th2值差异无统计学意义(P>0.05)。结论1,25D3对T1DM患者的GAD65反应性分泌IFN-γ的Th1细胞具有直接抑制作用,显著改善Th1/Th2的免疫失衡状态。Objective To explore immunomodulatory effects of 1 α,25-dihydroxyvitamin D3 on the balance of Th1/Th2 in type 1 diabetes （T1 DM）. Methods Six patients newly diagnosed as classic T1 DM and 6 healthy unrelated individuals matched for gender and age were investigated. Vitamin D receptors （VDR） was detected by indirect immunofluorescent staining. Human VDR protein expression modulated by 1,25-dihydroxyvitamin D3 was analyzed by Western blot,and enzyme linked immune spot （ELISPOT） assay was performed to measure the frequencies of IFN-γ, IL-4-secreting T cell, representing the frequencies of Thl and Th2, respectively. Results ①Not only did VDR present in T cell nucleus of T1DM, but also of healthy controls,whereas T cells of T1DM appeared to possess higher expression; ②The frequencies of Thl, Th2 and the ratio of Th1/Th2 were 18,3,6 in classic T1DM ,2. 5,3.5,0.71 in healthy control,and 5.6,4.5, 1.22 in T1DM after 72 hours treatment with 1α,25-dihydroxyvitamin D3, respectively. Compared with the healthy control, the frequencies of Thl and Th1/Th2 ratio in T1 DM group without 1 α,25-dihydroxyvitamin D3 treatment were remarkably increased, both P 〈 0. 01. After treatment with 1 α,25-dihydroxyvitamin D3, the Thl and Th1/Th2 ratio were markedly decreased,both P 〈 0.01. Whereas among the three groups, there were no differences in the frequency of Th2 ,P 〉0. 05 ;③1α,25-dihydroxyvitamin D3 may up-regulate VDR protein ofT cells in T1 DM. Conclusion 1 ct,25-dihydroxyvitamin D3 shows marked inhibitive effects on GAD65-reactive, IFN-γ-producing T cells in classic T1 DM, thus restoring the immune balance of Th1/Th2 in T1DM patients.

关 键 词：1α 25二羟维生素D3 糖尿病 1型 辅助性T淋巴细胞 酶联免疫斑点 

分 类 号：R587.1[医药卫生—内分泌]