环孢素A对心脏移植大鼠外周血单个核细胞免疫分子表达的影响

Effects of cyclosporinea A on the expression of immune molecules in peripheral blood mononuclear cells of the allogeneic heart transplantation rats

目的 通过对大鼠心脏移植 ,探讨环孢素A对免疫排斥反应过程中免疫分子表达的影响。方法 将大鼠分为 2组 ,用药组大鼠心脏移植术前后以 15mg·kg-1体重环孢素A灌胃给药 ;对照组灌胃给予同等体积的生理盐水。 2组分别在移植前、移植术后 1,3,7,10和 12d取血 ,用荧光单克隆抗体 (mAb)标记单个核细胞免疫分子 ,流式细胞仪检测MHC II,CD4 ,CD8,ICAM I和IL2 R的表达水平。结果 大鼠心脏移植前 ,环孢素A组外周血单个核细胞表面免疫分子CD4的表达水平明显低于对照组 ,移植术后 ,环孢素A组的CD4和ICAM I的正调表达时相出现于移植后的前 2 4h内 ,环孢素A组的CD8于移植后第 2 4小时至第 3天时 ,出现一个负调表达的低谷 ,这一负调表达期比对照组延长了 2d ,而环孢素A组CD8开始正调表达时相是移植后第 3天 ,比对照组正调表达时相晚 2d ,比同组CD4和ICAM I开始正调表达时相晚 2～ 3d ,比同组IL 2R开始正调表达时相晚 2d。结论 ①环孢素A不抑制急性器官移植排斥反应早期 (抗原呈递期 )外周血单个核细胞对MHC Ⅱ 抗原肽复合物的表达过程 ;②环孢素A不能有效抑制ICAM I的表达 ,而是促进其表达 ;③环孢素A不能有效抑制MHC Ⅱ 抗原肽和ICAM I通过TCR共同介导的CD4 + T单个核细胞激活过程 。

OBJECTIVE: To investigate the effect of cyclosporine A(CsA) on the expressions of immune molecules in peripheral blood mononuclear cells of the allogeneic heart transplantation rats. METHODS: Rats were divided into CsA experimental group, or control group and orally treated with CsA (15 mg &middot kg-1 weight) in CsA group or water in control group respectively. Mononuclear cells from peripheral blood were collected at 1,3,7,10 and 12 d after heart transplantation. Monoclonal antibodies were used to label surface molecules of cells. Immune molecules expression of MHC-II, ICAM-I, CD4, CD8 and IL-2R was separately evaluated by flow-cytometer. RESULTS: Compared to control group, CD4 immune molecules in cyclosporine A group decreased before heart transplantation. Within 24 h, CD4 and ICAM-I increased in cyclosporine A group after heart transplantation. However, CD8 was down-regulated from 24 h to 3 d after heart transplantation. The down-regulation was extended for 2 d in cycosporine A group compared with that in the control group. The increase of CD8 was observed from 2 d to 3 d. The increase was delayed for two days compared with that of CD4 and ICAM-I and was later 2 d than that of IL-2R in the CsA group. CONCLUSION: (1)DCsA did not effectively suppress MHC-II expression in the early period of post-transplantation rejection. (2) CsA didn't effectively repress ICAM-I expression but expedited it. (3)CsA didn't effectively repress CD4+ T cells activation featured by MHC-II, I-CAM-I and TCR intermedium. Simultaneity, CsA didn't effectively repress IL-2R expression. (4)CsA suspended CD8 expression.