小分子化合物J2对小鼠角膜移植术后植片RANTES基因表达的影响

摘要]目的研究小分子化合物J2对同种异基因小鼠角膜移植后植片RANTES基因表达的影响，从而探讨新型药物J2对于角膜移植排斥反应的作用机制。方法建立小鼠角膜移植模型，随机分为A、B、C、D四组。A组为自体原位移植组，B、C、D组均采用C57BL／6-BALB／c同种异体角膜移植模型，术后采用腹腔注射给药，自手术当日开始，A组、B组给予安慰剂，C组给予CsA10mg／kg，D组给予J215mg／kg，每天1次，连续给药12d。观察各组植片生存指数变化，分别在术后第1周、第2周、第3周、第4周行RT-PCR检测角膜植片中RANTES基因的表达。结果同种异体移植安慰剂组角膜植片平均存活时间为（18.87±4，19）d，J2组和CsA组发生排斥时间明显延迟，分别为（33.12±6.80）d和（35.13±5.74）d，与同种异体移植安慰荆组比较差异有显著性（P〈0.01），但J2组与CsA组比较差异无显著性。在正常小鼠角膜未见RANTES基因表达。自体移植组RANTES基因在第1周均有少量表达，而其他3周没有显著表达；异基因移植组从第1周开始表达各种基因，第3周表达明显增强；而CsA组和J2组从第1周开始表达，第2、第3周表达减弱，第4周表达强于前3周。结论RANTES基因参与了异基因小鼠角膜移植排斥反应，J2可以抑制其表达。

Effect of a micromolecular compound J2 on the expression of the RANTES gene in implants of mouse corneal allografts

Objective To investigate the effects of J2 on the prevention of allograft rejection. Methods One hundred C57BL/6 and 38 BALB/c mice were used as donors and recipients to estab- lish a corneal allograft model, and were randomly divided into groups A, B, C and D. Group A was the autograft control and group B was the allograft control and both control groups were giv- en only a placebo. Group C, the allograft group, was treated with intraperitoneal CsA （10 mg/kg/d） and group D, allograft group, was treated with intraperitoneal J2 （15 mg/kg/d） continuously for 12 days, beginning on the day of transplantation. A graft survival in- dex was noted for each group. At 1, 2, 3 and 4 weeks after the operation, corneal RANTES mRNA expression was detected by RT-PCR. Results The average survival rate of the transplant in the corneal allograft control group was （18.87±4.19）d. Treatment with J2 and CsA led to a prolonged survival rate of the grafts that was statistically significant （33.12±6.80）d and （35.13±5.74）d] （P〈 0.01）. But there was no significant difference between the J2 and CsA groups. RT-PCR results showed that, in the first week, few RANTES genes were expressed in the autologous transplant group, and were not significantly expressed in the remaining three weeks. RANTES genes were expressed from the first week in the allogeneic transplant group and significantly increased in the third week. RANTES genes were expressed from the first week in the CsA and J2 groups, and expression decreased in the second and third weeks. Expression in the fourth week was stronger than the other three weeks. Conclusion The RANTES gene was involved in mouse corneal allograft rejection; J2 can inhibit its expression.