ResolvinE1对高危角膜移植免疫排斥反应的抑制作用

发布时间：2018-03-04 10:36

  本文选题：ResolvinE1　切入点：高危角膜移植排斥反应　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:观察在高危角膜移植动物模型中,ResolvinE1(RvE1)对术后免疫排斥反应的抑制及延长角膜植片存活时间的作用。方法:采用随机数字表法将90只BALB/C小鼠分成异体角膜移植+生理盐水组(Control组)、异体角膜移植+RvE1组(RvE1组)及自体角膜移植组(Syngeneic组),每组各30只。以BALB/c小鼠为受体,C57BL/6小鼠为供体,受体右眼缝线法诱导2周后行穿透性角膜移植手术。在术后连续7天每日对Control组给予不含药物的生理盐水10ul结膜下注射,RvE1组给予ResolvinE1 1ug/10ul,Syngeneic组给予生理盐水10ul。在裂隙灯下观察小鼠角膜移植物透明情况并对其排斥反应进行评分。术后3周对移植物做HE染色,观察角膜病理学改变;采用免疫组化检测角膜CD4、IFN-γ及IL-17的表达;流式细胞术检测术眼侧颈部淋巴结Th1、Th17和Treg细胞的表达情况;荧光定量PCR法及CBA检测Th1、Th2及Th17细胞相关因子的表达水平。结果:RvE1组与Control组相比,植片存活时间明显延长,差异有统计学意义(P0.05)。RvE1组植片水肿程度、炎症细胞及CD4+T细胞(Th1/Th17)浸润程度较Control组明显减轻。术后3周,与Control组相比,RvE1组术眼测引流淋巴结中Th1细胞、Th17细胞比例明显减少;植片中IL-1α,IL-1β,TNF-α,IL-2,IL-6,IFN-γ,IL-17A,IL-17F,IL-21和IL-22 mRNA水平明显降低,IL-2,TNF,IL-6,IFN-γ和IL-17蛋白水平也显著降低(差异均有统计学意义)。然而,RvE1组引流淋巴结中Treg细胞比例较Control组无明显改变,IL-4,IL-5和IL-10细胞因子水平亦无明显差异。结论:一、ResolvinE1可抑制高危角膜移植术后免疫排斥反应,减少植片水肿及炎症细胞的浸润,延长植片存活时间。二、Resolvin E1可能是通过下调Th1/Th17细胞相关的炎症反应来达到抑制免疫排斥的作用。三、ResolvinE1可能不是通过上调Treg细胞相关的免疫赦免反应来达到抑制免疫排斥的作用。
[Abstract]:Objective: to observe the inhibitory effect of ResolvinE1 (RvE1) on postoperative immune rejection and prolong the survival time of corneal graft in high risk corneal transplantation animal model. Methods: 90 BALB/C mice were divided into allograft keratoplasty by random number table. Normal saline group, allograft RvE1 group (RvE1 group) and autogenous cornea transplantation group (30 rats in each group). BALB/c mice were used as recipients of C57BL / 6 mice. Penetrating keratoplasty was performed 2 weeks after suture induction in the right eye of the receptor. After 7 days of operation, the Control group was given normal saline 10ul without drugs, and the RvE1 group was given ResolvinE1 1ugr / 10ulu Syngeneic group, and the ResolvinE1 1ugr / 10ulu Syngeneic group was given normal saline 10ul. in the slit-lamp group, the patients in the RVE1 group were treated with normal saline 10ul daily. The grafts were stained with HE at 3 weeks after operation. The expression of IFN- 纬 and IL-17 were detected by immunohistochemistry and Th1T17 and Treg cells in lateral cervical lymph nodes were detected by flow cytometry. Fluorescence quantitative PCR and CBA were used to detect the expression of Th1Th _ 2 and Th17 cell related factors. Results the survival time of grafts in the group of RvE1 was significantly longer than that in the group of Control, and there was significant difference in edema of grafts in the group of P0.05-RvE1. The infiltration degree of inflammatory cells and CD4 T cell Th1 / Th17 was significantly less than that of Control group. 3 weeks after operation, compared with Control group, the percentage of Th1 cell Th17 cells in the drainage lymph nodes of RvE1 group was significantly lower than that in Control group. The levels of IL-17FU IL-21 and IL-22 mRNA of IL-17An IL-17FU IL-21 and IL-22 mRNA in grafts were significantly lower than those in Control group. (all the differences were statistically significant. However, there was no significant change in the percentage of Treg cells in lymph node drainage in RvE1 group compared with Control group, and there was no significant change in IL-4 IL-5 and IL-10 cytokine levels in the RvE1 group, nor did the level of IL-4 IL-5 and IL-10 cytokines in the RvE1 group. The level of IL-4 IL-5 and IL-10 cytokines in the RvE1 group was not significantly changed compared with that in the Control group. Conclusion: ResolvinE1 can inhibit the immune rejection after high risk corneal transplantation. Reduce graft edema and inflammatory cell infiltration, It is suggested that the inhibition of immune rejection may be achieved by down-regulating the inflammatory response of Th1/Th17 cells, while ResolvinE1 may not inhibit immune rejection by upregulating the immune amnesty response associated with Treg cells.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R779.65

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