重组hIL-10抗家兔皮肤移植反应中CC、IL-8/CXCL8趋化因子的变化

The changes of CC,IL-8/CXCL8 chemokine in the reaction of rhIL-10 resisting the skin graft

目的:检测家兔皮肤移植经rhIL-10作用后,血清中CC、IL-8/CXCL8趋化因子的变化,探讨CC、IL-8/CXCL8趋化因子在rhIL-10抗免疫排斥机制中的作用。方法:皮肤移植家兔分6组:①rhIL-10低剂量,②rhIL-10高剂量,③CsA低剂量,④CsA高剂量,⑤rhIL-10+CsA低剂量联合和⑥生理盐水组;每只家兔均于术前1天开始肌注给药,连续注射10天;各组分别于术前1天、术后1、4、7、14、21、28天取外周血,分离血清,以ELISA法检测移植家兔血清CC、IL-8/CXCL8趋化因子水平。结果:(1)术后各组IL-8水平均升高,术后4天、7天⑥组IL-8水平高于各组(P<0.05)。(2)术后各组MCP-1水平明显升高,术后1天、4天,⑥组MCP-1水高于各组(P<0.05),术后7天⑥组MCP-1水平高于①组、⑤组(P<0.05);术后7天、14天CsA抑制组高于联合组(P<0.05)。(3)术后各组MIP-1α明显升高,术后4天⑥组MIP-1α水平高于①、③、⑤组,术后7天⑥组MIP-1α水平高于各组(P<0.05);(4)术后各组MIP-1β水平升高,但同时间段组间比较差异无统计学意义(P>0.05)。结论:CC、IL-8/CXCL8趋化因子在皮肤移植后明显升高,表明在急性排斥反应中发挥了重要作用,随排斥反应加重而进一步增高,皮片排斥后下降,可作为观察和诊断移植排斥的合适标志物。

Objective：To analyze the dynamic changes of CC,IL-8/CXCL8 chemokine in the serum drew from skin graft rabbits which treated with rhIL-10,and to explore the mechanism of rhIL-10 resisting the immune rejection.Methods：The recipient rabbits were randomly divided into six groups： ①：rhIL-10 5 μg/（kg·d）;②：rhIL-10 10 μg/（kg·d）;③：CsA 5 mg/（kg·d）;④：CsA 10 mg/（kg·d）;⑤：rhIL-10 5 μg/（kg·d） and CsA 5 mg/（kg·d）;⑥：NS 1 ml/d.Giving the medicine 1 day preoperation and use consecutively 10 days by intramuscular injection.Dynamic serum levels of CC,IL-8/CXCL8 chemokines were analyzed by ELISA method 1 d preoperation and 1,4,7,14,21,28 d postoperation.Results：（1）IL-8 serum level in all groups were increased after skin graft,and it in saline control group was significantly higher than in any other groups on postoperative days（PODs）4,7（P0.05）.（2） MCP-1 serum level in all groups were increased after skin graft,and it in saline control group was significantly higher than in any other groups on POD1 and 4（P0.05）,as well as higher than in ① and ⑤groups on POD7（P0.05）.Besides,it in CsA groups were significantly higher than in combination group on POD7 and 14（P0.05）.（3） MIP-1α serum level in all groups were increased after skin graft,and it in saline control group was significantly higher than in group ①,③ and ⑤ on POD4,as well as significantly higher than in any other groups on POD7（P0.05）.（4） MIP-1β serum level in all groups were increased after skin graft.Conclusion：The expression of CC,IL-8/CXCL-8 chemokines in all groups have been up-regulated after skin allograft hinted that they play important roles in the process of acute rejection.There is a close correlation of serum CC,IL-8/CXCL8 chemokine level with acute allograft rejection,suggesting that they could be regarded as valuable signals of acute allograft rejection.