Foxp3,IDO在小鼠角膜移植免疫排斥反应的表达

Expression levels of Foxp3 and indoleamine 2,3-dioxygenase in mouse corneal allograft rejection

背景:移植免疫反应是导致角膜移植术后失败的主要原因,但其具体发病机制不明确。有研究报道,Foxp3和吲哚胺2,3-二氧化酶(indoleamine 2,3-dioxygenase,IDO)与移植免疫有关。目的:研究Foxp3,IDO在小鼠角膜移植免疫排斥反应中的作用。方法:以C57BL/6小鼠为供体,BALB/c小鼠为受体建立角膜移植实验模型。将30只BALB/c小鼠随机分为3组,正常组6只;角膜移植组12只;地塞米松治疗组12只。角膜移植组:给予生理盐水;地塞米松治疗组:给予地塞米松注射液10 mg/kg,分别于角膜移植术后0,2,4,6,8,10 d经腹腔注射给药。用裂隙灯观察移植排斥情况,免疫组织化学检测植片γ-干扰素表达,Real-time PCR检测植片内Foxp3 mRNA,IDO mRNA的表达。结果与结论:(1)地塞米松治疗组发生排斥反应时间(20.667±1.033)d,较角膜移植组(14.833±1.472)d明显延迟(P<0.05);(2)角膜移植组术后第14天角膜植片内γ-干扰素及Foxp3 mRNA,IDO mRNA的表达较地塞米松治疗组明显增强(P<0.05);(3)结果提示,γ-干扰素及Foxp3,IDO在角膜移植免疫排斥反应过程中发挥重要的作用,降低角膜植片γ-干扰素及Foxp3,IDO表达可能有助于诱导耐受。

BACKGROUND： Immunological rejection reaction is the main cause of corneal allograft failure and its pathogenesis is still unclear. Foxp3 and indoleamine 2,3-dioxygenase（IDO） are reported to be associated with transplantation immunity. OBJECTIVE： To study the roles of Foxp3 and IDO in mouse corneal allograft rejection. METHODS： Routine penetrating keratoplasty was performed with C57 BL/6 mice as donors and 30 BALB/c mice as recipients. The recipient mice were randomly divided into normal group（n=6）, allograft group（intraperitoneal injection of normal saline solution for 6 times at 0, 2, 4, 6, 8 and 10 days after allograft, n=12） and dexamethasone group（intraperitoneal injection of 10 mg/kg dexamethasone, n=12）. The graft rejection was evaluated under slit lamp microscope. Expression level of interferon-γ in grafts was detected by immunohistochemical staining. The expression levels of Foxp3 and IDO mRNA in grafts were detected by real-time PCR. RESULTS AND CONCLUSION： The mean graft survival time in the allograft group was（14.833±1.472） days, and that in the dexamethasone group was（20.667±1.033） days（P〈0.05）. The expression levels of interferon-γ as well as Foxp3 and IDO mRNA in grafts were significantly increased in the allograft group compared with the dexamethasone group（P〈0.05） at the 14^（th） day postoperatively. These results suggest that Foxp3, IDO and interferon-γ play important roles in corneal allograft rejection; therefore, decreasing the expression levels of Foxp3, IDO and interferon-γ may contribute to inducing tolerance.