趋化因子受体CCR5在同种大鼠心脏移植局部的表达

CCR5 expression in cardiac allograft in rats

目的探讨急性排斥反应过程中CCR5基因与蛋白在移植心脏局部表达的意义及环孢素(CsA)的影响。方法施行大鼠异位心脏移植术,移植大鼠分为3组,每组45只,对照组5只:SD大鼠间的移植为同系移植组(A组),Wistar至SD大鼠的移植分为未用CsA干预组(B组)及CsA干预组(C组),健康SD大鼠为对照组。分别采用RT-PCR方法和免疫组化方法检测CCR5 mRNA和蛋白的表达。结果CCR5 mRNA在A组各时间点和对照组均呈阴性表达,在B组的表达变化与急性排斥反应的进程相关,术后第3天CCR5 mRNA表达上调至峰值(1.4±0.33);C组应用CsA后,CCR5 mRNA表达峰值(0.5±0.29)显著低于B组(t=2.11,P<0.05)。CCR5蛋白定位于移植心脏间质单个核浸润细胞。结论CCR5基因与蛋白的表达上调与急性排斥反应过程中移植物间质CCR5阳性单个核细胞浸润密切相关,可能为急性排斥反应的早期诊断提供帮助;CsA抑制CCR5阳性细胞的浸润及CCR5的表达水平。

Purpose To investigate the expression of chemokine recepoor 5 （CCR5） in cardiac allografts and the effect of cyclosporin A（CsA）. Methods Three groups of rats were performed heterotopic cardiac transplantation with 45 rats in each group and 5 rats in the control group. SD to SD transplantation was isograft group （A group）,Wister to SD transplantation was allograft group which was further divided into CsA untreated allograft group （B group） and CsA treated allograft group （C group）. Healthy SD rats were used in the normal control group. CCR5 mRNA expression was detec- ted by one-step RT-PCR method and the expression of CCR5 protein was detected by standard ABC immunohistochemical technique. Results CCR5 mRNA negatively expressed in both isografts and normal heart specimens. The variation of CCR5 mRNA expression correlated with the process bf acute allograft rejection. The peak of CCR5 mRNA expression （1.4 ± 0.33） appeared on the third day after transplantation and it was significantly downregulated by CsA （t = 2. 11, P〈0.05）. Immunohistochemical staining assay confirmed the presence of CCR5 ＋ mononuclear cells in allografts. Conclusions Upregulation of CCR5 in allograft correlates significantly with the trafficking of mononuclear cells, which may assist diagnosis of acute allograft rejection. CsA inhibits infiltration of CCR5 positive mononuclear cells and expression of CCR5 on the cell surface.