小鼠MD-1表达的影响因素及其在移植排斥反应中的作用  

Factors affecting MD-1 expression and role of MD-1 on rejection in mice

作　　者：张鑫[1] 陈忠华(指导) 

机构地区：[1]华中科技大学同济医学院同济医院器官移植研究所,国家教育部器官移植重点实验室,国家卫生部器官移植重点实验室,武汉430030

出　　处：《中国免疫学杂志》2005年第6期444-448,共5页Chinese Journal of Immunology

基　　金：本课题受国家973计划专项基金(2003CB515505)资助

摘　　要：目的:探讨影响小鼠MD-1表达的因素以及MD-1在移植排斥反应中的作用。方法:实验采用C57BL/6-BALB/c小鼠同种皮肤移植模型,以非特异性免疫抑制剂CsA、FK506、MMF和SRL,以及特异性MD-1反义脱氧寡核苷酸(AS-ODNs)为干预手段,于术后第11天留取标本检测脾细胞MD-1表达水平和增殖反应强度、血清IL-2和IL-10水平以及皮肤移植物组织学改变,并记录移植物存活时间。结果:CsA、MMF和AS-ODNs处理能减少脾脏MD-1表达阳性细胞数、降低脾细胞增殖反应强度、下调血清IL-2水平和上调IL-10水平,并显著延长皮肤移植物平均存活时间(MST);FK506与CsA和MMF处理结果的差异在于其对血清IL-10水平无明显影响;SRL处理仅能减低脾细胞增殖反应强度和延长皮肤移植物MST,对MD-1表达及IL-2与IL-10分泌无明显影响。MD-1表达水平与脾细胞增殖反应强度和血清IL-2水平呈极显著正相关,和IL-10水平呈极显著负相关。结论:CsA、FK506、MMF和AS-ODNs处理均能有效抑制小鼠MD-1的表达。免疫抑制剂干预MD-1表达的作用与血清IL-2水平下调有关。MD-1通过影响淋巴细胞增殖反应和血清IL-2、IL-10水平,在移植排斥反应中发挥重要作用。Objective:To investigate the factors affecting MD-1 expression and the role of latter played on rejection in mice.Methods: C57BL/6 to BALB/c skin allograft model was employed in all groups,followed by non-specific immunosuppressants CsA,FK506,MMF and SRL i.p. ,as well as specific antisense oligodeoxynucleotides(AS-ODNs) i.v..Recipients were sacrificed at 11 days after transplantation.MD-1 expression was determined by FACS. AlamarBlue was used to evaluate the proliferation of recipient splenocytes. Serum levels of IL-2 and IL-10 were detected by ELISA. Results:Compared with saline controls, the mean survival times(MST) of skin allografts in all of the immunosuppressants and AS-ODNs treated groups were significantly prolonged(P<0.05).CsA,MMF and AS-ODNs inhibited MD-1 expression and lymphocyte proliferation,as well as decreased serum level of IL-2 and increased that of IL-10;FK506 treatment show all of the effects mentioned above but up-regulated IL-10 level;SRL had no significantly influence upon MD-1 expression,IL-2 and IL-10 level,although also supressed prolifera tion(P<0.05.vs controls).The negative correlation between MD-1 expression and lymphocyte proliferation or EL-2 level,and the positive correlation between it and IL-10 level were significant(P<0.01).Conclusion: CsA, FK506, MMF and AS-ODNs efficiently inhibited MD-1 expression.The effects of non-specific immunosuppressants were seemly associated with down-regulatory of serum level of IL-2. MD-1 played a really important role on rejection by affecting lymphocyte proliferation as well as IL-2 and IL-10 production.

关 键 词：MD-1 免疫抑制剂 反义脱氧寡核苷酸 

分 类 号：R392.45[医药卫生—免疫学]