小剂量环孢素A对大鼠同种异体肢体移植的免疫抑制作用

Immunosuppression by low dose cyclosporin A in rat limb allotransplantation: an experimental study

目的通过大鼠同种异体肢体移植模型,分析小剂量环孢素A(cyvlosporinA ,CsA)对大鼠同种异体肢体移植急性排斥反应的免疫抑制作用。方法采用雄性Wistar和SD大鼠为供、受体,以CsA为免疫抑制剂。对照组14只,将Wistar大鼠肢体移植至SD大鼠,术后不用药。实验组术后按用药剂量的不同分为2组( 2mg/kg组17只大鼠和CsA 6mg/kg组18只大鼠)。2组术后用药时间均为4周(每日1次共2周,然后每周2次共2周)。术后观察大鼠一般情况、移植肢体排斥反应及存活时间;用免疫荧光染色流式细胞仪检测各组手术前后T细胞亚群的变化。结果对照组移植肢体平均存活时间为[( 7.0 0±0 .78)d , x±s ,下同] ;CsA 2mg/kg组为( 3 7.18±0 .5 1)d ,CsA 6mg/kg组为( 3 3 .2 0±1.0 5 )d。术后第3天,对照组的CD4/CD8比值显著增高,移植肢体开始出现肿胀、皮肤红斑等表现。实验组的CD4/CD8较术前无明显变化。结论小剂量CsA能抑制大鼠同种异体肢体移植术后急性排斥反应的发生,并能延长移植肢体的存活时间。

Objective To study the immunosuppressive effect of low dose cyclosporin A in rat limb allotransplantation. Methods 49 male SD rats were used as recipients and randomly divided into 3 groups according to different postoperatve immunosuppressive regime. Wistar rats were used as donors. Limb transplantation from Wistar rats to SD rats were performed. In the control group (n=14) no immunosuppressives were given following allotransplantation. In experimental group 1 (n=17) and group 2 (n=18) 2mg/kg CsA and 6mg/kg CsA were given for 4 weeks, respectively. To evaluate the results, circulation of the transplantated limb, the mean rejection time, histologic grading of skin rejection of limb grafts and survival time of limb grafts were observed. Changes of T lymphocyte subsets were examed by immunofluorescence staining and flow cytometry. Results In the control group rejection signs (edema and erythema of the skin) appeared after an average of 3.36±1.15 days following allotransplantation.The relative value of CD_4/CD_8 was obviously increased, being related to the degree of rejection. The mean survival time of the allografts was only 7±0.78 days. In the experimental groups the graft survival time was prolonged, being 37.18±0.51 days for group 1 and 33.20±1.05 days for group 2. Relative value of CD_4/CD_8 had no marked change as compared to preoperative level. Conclusion Low dose cyclosporin A is a potent immunosuppressive agent in preventing the acute rejection of limb allografts. It can obviously prolong the survival time of limb grafts.