未成熟树突状细胞诱导Th1／Th2偏移抑制大鼠高危角膜移植排斥反应的实验研究  

Inhibiting high-risk corneal allograft rejection by Th1/Th2 imbalance induced by immature dendritic cells in rats

作　　者：付燕[1,2] 高晓唯[2] 王梦斐[2] 杜安杰[1] 李霞[2] 赵旭东[2] 

机构地区：[1]石河子大学医学院,新疆维吾尔自治区石河子市830002 [2]解放军474医院全军眼科中心,新疆维吾尔自治区乌鲁木齐市830013

出　　处：《眼科新进展》2013年第3期220-224,共5页Recent Advances in Ophthalmology

基　　金：军区医药卫生科研项目资助(编号:CLZ11JA25)~~

摘　　要：目的研究供体来源的未成熟树突状细胞(immature dendritic cell,imDC)对高危角膜移植免疫排斥反应的抑制作用及其机制。方法以45只SD大鼠为受体,23只Wist-ar大鼠为供体,碱烧伤建立同种异体高危角膜移植模型。受体SD大鼠随机分为对照组、imDC组、成熟树突状细胞(mature dendritic cell,mDC)组,每组15只;对照组:术前7d经尾静脉注射PBS液0.1mL;imDC组:于术前7d经尾静脉注射体外培养的供体骨髓来源的imDC106个;mDC组:于术前7d经尾静脉注射体外培养的供体骨髓来源的mDC106个。术后每天裂隙灯观察各组角膜植片存活情况并评分;于术后14d每组随机处死5只大鼠,RT-PCR检测角膜植片Th1/Th2细胞因子白细胞介素(interleukin,IL)-12、IL-15、IL-18、IL-4、IL-10mRNA表达水平。结果 imDC组角膜植片存活时间为(19.8±2.1)d,较对照组的(9.2±1.9)d和mDC组的(7.9±1.4)d显著延长,差异均有统计学意义(均为P<0.01)。RT-PCR结果显示,imDC组Th1型细胞因子IL-12、IL-15、IL-18mRNA表达较对照组和mDC组明显降低;Th2型细胞因子IL-4、IL-10mRNA表达明显升高。结论体外培养的供体来源的imDC可以抑制大鼠同种异体高危角膜移植免疫排斥反应,而调节受体Th1/Th2细胞因子比例是其降低大鼠角膜移植术后免疫排斥反应的机制之一。Objective To investigate the suppressive effects of immature den- dritic cells （imDC） derived from donor bone marrow on rat high-risk corneal allograft rejection and explore its mechanisms. Methods Wistar and SD rats were used as do- nors and recipients, respectively. Forty-five SD rats were randomly divided into control group ,imDC group and mDC group, 15 rats in each group. High-risk corneal allograft re- jection models were induced by alkaline burn. In control group, SD rats only received corneal transplantation;In imDC group, donor bone marrow-derived imDC of 10^6 were injected into SD rats via tall vein before corneal transplantation;In mDC group, donor bone marrow-derived mDC of 10^6 were injected into SD rats via taft vein before corneal transplantation. The corneal grafts survival in each group were observed and scored by slit lamp. In each group, five recipients were killed on the 14th day after transplantation, RT-PCR was used to detect the mRNA expression of Thl-type cytokine IL-12 ,IL-15 ,IL- 18 and Th2-type cytokine IL-4,IL-10. Results The survival time of corneal grafts was （ 19.8 ± 2.1 ） days in imDC group, （9.2 ±1.9 ） days in control group and （7.9± 1.4 ） days in mDC group, there were statistical differences（ both P 〈 0.01 ）. The expressions of IL- 12, IL-15 and IL-18 in imDC group were obviously lower than those in control group and mDC group,but the expressions of IL-4 and IL-10 were higher. Conclusion The pre- treatment with imDC can prolong the survival time of rat corneal graft after transplanta- tion. The mechanism of immune tolerance induced by imDC might be influenced by the balance of Th1/Th2 cytokines.

关 键 词：未成熟树突状细胞 角膜移植 免疫耐受 TH1 TH2 

分 类 号：R779.65[医药卫生—眼科]