ICOS/B7RP-1共刺激通路在大鼠慢性移植物失功中作用的研究

目的研究阻断ICOS/B7RP-1共刺激通路对慢性移植物失功的抑制作用,并探讨其可能的机制。方法建立大鼠慢性移植物失功的模型,将实验动物分为四组：A组：假手术组;B组：同基因移植组;C组：同种异体移植组（对照组）;D组：抗-ICOS单抗注射组。各组动物移植后用CsA10mg/kg·d10天避免急性排斥,D组于术后10天后开始运用抗-ICOS单抗2mg/kg腹腔注射,2次/周至术后90天,分别于术后4w、8w、12w处死大鼠,处死大鼠前抽血查血肌酐,观察肾功能改变情况;取移植肾进行病理学观察,用免疫组织化学法和实时荧光定量PCR检测ICOS蛋白和mRNA在组织中的表达及定位。结果假手术组和同基因移植组大鼠术后长期存活,两组各观察指标无明显变化。对照组大鼠各时间段移植肾脏Banff评分总分较假手术组和同基因组明显增高,移植肾CAN改变明显。抗ICOS抗体干预后12周时移植肾肾小球可见轻微硬化,肾小管部分扩张,较对照组明显减轻。免疫组织化学和荧光定量PCR结果表明,抗ICOS抗体组大鼠移植肾中ICOS的表达较对照组明显降低。结论阻断ICOS/B7RP1共刺激通路具有明显的抗移植物慢性损伤的作用。

Function of ICOS/B7RP-1 costimulation in chronic allograft nephropathy of rat

Objective To study the efficacy of blockade of ICOS/B7RP-1 in treatment of rat chronic allograft nephropathy. Methods Orthotopic kidney transplantation was performed following the procedure of Kamada with our modification. All of experimental rats were divided into four groups.Group A: pseudo-operation group; group B: isograft group; group C: control group (CAN group);group D: anti-ICOS antibody group (intraperitoneai injection of anti-ICOS antibody 2mg/kg twice weekly). The Serum creatinine level and pathological changes according to Banff Standards were observed at the 4th, 8th and 12th weeks post-transplantation. The immunohistochemistry and real-time quanti-tative PCR were used to detect localization and expression of ICOS in transplant kidney. Results All rats in group A and group B were survival for a long time; there were no significant difference between them. The pathological changes of CAN in control group were significant, and the score according to Banff Standards in control group was higher than in other groups. Anti-ICOS treatment led to a signifi-cant decrease of chronic rejection lesions. The expression of ICOS in group D was down-regulated than that in group C. Conclusions Blockade of ICOS-B7RP-1 with anti-ICOS-antibody may attenuate remarkably the development of CAN.