外周血单个核细胞CXCR3 mRNA表达与大鼠心移植急性排斥的关系

Relationship between CXCR3 mRNA expression of peripheral blood mononuclear cells and acute cardiac rejection in rats

目的探讨外周血单个核细胞(PBMC)趋化因子受体CXCR3mRNA动态变化与大鼠心移植急性排斥的关系及其在早期诊断中的价值。方法以Wistar和SD大鼠作为供体,SD大鼠作为受体,建立腹部异位心脏移植模型,按移植前后处理方法不同随机分3组:A组为SD大鼠同基因移植对照组,移植前后未作处理;B组为Wistar-SD急性排斥组,移植前后未作处理;C组为Wistar-SD异基因移植治疗组,移植日开始给予环胞素A(CsA)5mg/kg/d腹腔注射×14d。术后第1、3、5、7d分批处死,采用实时定量PCR检测PBMC的CXCR3mR-NA表达,并对心肌进行病理组织学检查,每组留5只用于观察生存期。结果A组大鼠移植心存活时间均大于100d,B、C组分别为(7.40±1.14)d、(24.00±2.35)d,C组较B组存活时间明显延长(P<0.01),A组较B、C组存活时间更长(P<0.01)。A组各时间点均未发生排斥反应,PBMC的CXCR3mRNA呈低水平表达;B组术后PBMC的CXCR3mRNA动态变化与急性排斥反应的进程呈正相关,术后5d PBMC的CXCR3mRNA表达上调至峰值4.30±0.82;C组经环胞素A治疗后排斥反应发生率明显下降,各时间点PBMC的CXCR3mRNA表达明显低于B组,术后7d达到峰值1.50±0.76,与B组相比差异具有显著性(t=7.08,P<0.01)。结论PBMC的CXCR3mRNA表达与排斥反应密切相关,提示可作为诊断急性排斥反应或者观察抗排斥反应疗效的指标。

Purpose To evaluate the role of chemokine receptor CXCR3 mRNA expression of peripheral blood mononuclear cells （PBMC） for prediction of early acute cardiac rejection in rats. Methods Three groups of rats underwent heterotopic cardiac transplantations：the donor and receptor of group A were both SD rats, untreated after transplant and served as control group. Group B and C underwent Wistar to SD transplantation,group B was untreated and group C was treated with Cyclosporine A （5 mg · kg^-1 ·d^-1, i. p. × 14 d）. The rats of three groups were killed at day 1,3,5 and 7 after transplant,peripheral blood and cardiac allograft were harvested. In each group 5 rats were left to be observed for survival time of cardiac allograft. CXCR3 mRNA was detected by real-time PCR. Cardiac allograft specimens were assessed pathologically. Results Survival time in group A was longer than 100 d and the average survival time in group B and C was （7. 40 ± 1. 14）d and （24. 00 ± 2.35）d. Compared with group B, the average survival time in group C was obviously prolonged（P〈0.01）. The average survival time in group A was much longer than group B and C（P〈0.01）. There was no rejection in group A and CXCR3 mRNA of PBMC was weakly expressed. There was a positive correlation between the dynamic change of CXCR3 mRNA of PBMC and the proccess of acute rejection in group B. The peak of CXCR3 mRNA expression 4.30 ± 0.82 in group B appeared in day 5 after transplant, while the peak expression was 1.50 ± 0.76 in group C which appeared in day 7 after transplant, significantly lower than group B （t = 7.08, P〈0.01）. Conclusions CXCR3 mRNA expression of PBMC was correlated with process of acute rejection,it maybe a new target in the diagnosis or therapy of acute cardiac rejection.