白细胞介素10基因转染抑制小鼠心脏移植排斥反应的实验研究

Effect of IL-10 gene transfer on cardiac allograft rejection in mice

目的 探讨白细胞介素 1 0 (IL 1 0 )基因转染对小鼠心脏移植排斥反应的抑制作用。方法 采用小鼠颈部心脏移植模型。随机将心脏移植后的小鼠分为 4组 :(1 )对照组 :心脏移植后每天用生理盐水 1ml灌胃 ;(2 )环孢素A(CsA)组 :心脏移植后每天用CsA 5mg/kg 灌胃 ;(3)IL 1 0组 :心脏移植时用IL 1 0重组腺病毒 30 0 μl(腺病毒滴度为 5× 1 0 1 1 pfu/ml)经主动脉根部灌注小鼠供心。(4)IL 1 0 +CsA半剂量组 :在IL 1 0组的基础上 ,每天用CsA 2 .5mg/kg灌胃。观察移植心脏的存活时间及心脏跳动情况。结果 IL 1 0组、IL 1 0 +CsA半剂量组和CsA组移植心脏存活时间均较对照组显著延长 (P <0 .0 1 ) ;IL 1 0组移植心脏存活时间较CsA组明显延长 (P <0 .0 5 ) ;IL 1 0 +CsA半剂量组移植心脏存活时间最长 ,优于IL 1 0组 (P <0 .0 5 )和CsA组 (P <0 .0 1 )。结论 IL 1 0基因转染对心脏移植排斥反应有较强的免疫抑制作用 ,可明显延长移植心脏的存活时间 ,并且与CsA有协同作用 ,共同应用时 ,可减少CsA的用量。

Objective To study the effect of interleukin-10 (IL-10) gene transfer on cardiac allograft rejection in mice.Methods The model of mice cervical heterotopic heart transplantation was set up. The isolated donor heart was transfected with IL-10 for 1 h, then transplanted to recipient. Sixty-four heart transplanted mice were divided into 4 groups randomly: control group (normal saline 1 ml per day), CsA group (CsA 5 mg/kg per day), IL-10 group [IL-10 adenovirus vector (5×10 11 pfu/ml) 300 μl], and IL-10 +CsA group[IL-10 adenovirus vector (5×10 11 pfu/ml) 300 μl and CsA 2.5 mg/kg]. Grafts survival days and transplanted heart beating conditions were observed every day after heart transplantation.Results In IL-10 group, CsA group and IL-10+CsA group, the survival time of the grafts was prolonged significantly as compared with control group, especially in IL-10+CsA group (P< 0.01). In IL-10 group, the survival time of the grafts was prolonged significantly as compared with CsA group (P< 0.05). In IL-10+CsA group, the survival time of the grafts was increased significantly as compared with IL-10 group (P< 0.05) and CsA group (P< 0.01). Conclusions IL-10 gene transfer could suppress cardiac allograft rejection. It could prolong the survival days of transplanted hearts. IL-10 gene transfer in combination with CsA could reduce the dose of CsA.