吗替麦考酚酯抑制小鼠TH17细胞的分化和增殖  

Mycophenolate mofetil suppresses differentiation and proliferation of helper T cells 17 in mice

作　　者：庄垟垟[1] 杨梅[2] 张岩[1] 龚淑文[1] 王芳[1] 陈必成[1] 夏鹏[1] 杨亦荣[1] 郑少玲[1] 

机构地区：[1]温州医学院附属第一医院移植中心,浙江省温州市325000 [2]温州医学院附属第一医院重症监护室,浙江省温州市325000

出　　处：《中华器官移植杂志》2011年第12期749-751,共3页Chinese Journal of Organ Transplantation

基　　金：基金项目：浙江省自然科学基金（Y2110944）;温州市科技计划项目（Y20100188）

摘　　要：目的通过观察吗替麦考酚酯（MMF）对小鼠辅助性T淋巴细胞17（TH17细胞）分化和增殖的影响，探讨MMF的免疫抑制作用及其机制。方法采用随机数字表法将小鼠分为MMF组与对照组，每组8只。MMF组小鼠每天给予MMF40mg·kg-1·d-1灌胃，对照组小鼠每天给予等体积生理盐水灌胃。3周后取小鼠外周血和脾脏，采用流式细胞术检测小鼠外周血和脾细胞中TH17细胞和CD4＋CD25＋调节性T淋巴细胞（Treg细胞）的比例，并计算出TH17细胞与Treg细胞的比值；采用酶联免疫吸附试验法分别检测两组小鼠血清中白细胞介素（IL）-17和IL-23的浓度。结果MMF组外周血和脾细胞中TH17细胞比例分别为（1．95±0．08）％和（2．42±0．06）％，对照组分别为（3．19±0．07）％和（4．21±0．25）％，两组比较，差异均有统计学意义（P〈0．05）。MMF组外周血和脾细胞中TH17细胞与Treg细胞的比值均显著低于对照组（P〈0．05）。MMF组小鼠血清IL-17水平明显低于对照组（P〈0．05），而血清IL-23水平高于对照组（P〈0．05）。结论MMF能够明显抑制小鼠体内TH17细胞的分化与增殖，降低TH17细胞与Treg细胞的比值，减少IL-17的分泌，有利于诱导免疫耐受。Objective To observe the effects of mycophenolate mofetil （MMF） on the differentiation and proliferation of Helper T cells 17 （TH 17）, so as to reveal its role and the possible mechanism in inducing immunological suppression. Methods Sixteen Balb/c mice of SPF level aged 8 weeks were randomly divided into two groups： MMF group and control group, with 8 mice in each group. In MMF group, the mice received intragastric administration of MMF （40 mg·kg-1·day-1）, and those in control group received intragastric administration of identical volumetric saline every day. After three weeks, peripheral blood was collected and spleen cells were prepared. Flow cytometry was used to determine the proportions of CD4＋ TH 17 and CD4＋ CD25＋ Tregs, then the ratio of TH 17/ Tregs was calculated, and the concentrations of interleukin-17 （IL-17） and interleukin-23 （IL-23） in serum were measured by ELISA. Results The proportion of CD4＋ TH 17 in the peripheral blood and spleen was （1.95±0.08） and （2.42±0.06） in MMF group, and （3.19±0.07）% and （4.21 ± 0. 25）% in control group, respectively. There were significant differences between the two groups （P 〈0. 05）. Meanwhile, the ratio of TH 17/Tregs in MMF group, both in the peripheral blood and spleen, was significantly decreased as compared with the control group （P〈0. 05）. The concentration of IL-17 in MMF group was lower, but that of IL-23 in MMF group was higher than in the control group （P〈0. 05）. Conclusion MMF could obviously suppress the differentiation and proliferation of CD4＋ TH 17 in vivo, reduce the ratio of TH17/Tregs and the IL-17 secretion, thus facilitate the induction of immune tolerance.

关 键 词：小鼠 TH17细胞 吗替麦考酚酯 细胞分化 细胞增殖 

分 类 号：R965[医药卫生—药理学]