摘要
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.
作者
宫玉波
刘勇
赵宏伟
许倩倩
郭惠玲
Gong Yu-bo;Liu Yong;Zhao Hong-wei;Xu Qian-qian;Guo Hui-ling(Department of Ophthalmology,the 306th Hospital of PLA,Beijing 100101,China;Department of Ophthalmology,Air Force General Hospital,Beijing 100142,China)
出处
《中国组织工程研究》
CAS
北大核心
2018年第28期4513-4517,共5页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金(30973245)~~