Study on effect of TLRs in rejection reaction after penetrating keratoplasty
Study on effect of TLRs in rejection reaction after penetrating keratoplasty
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发表时间：
2010
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通讯作者：
K. Xiong
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作者：
K. Xiong
Toll样受体（Toll like receptors，TLRs）可启动天然免疫，进而诱导获得性免疫，但TLRs能否识别外源性免疫因子介导器官或组织移植后的免疫排斥反应尚未见报道。36只SPF级Wistar大鼠作为供体，36只受体大鼠行同种异体角膜移植，72只受体大鼠行同种异体角膜移植，36只大鼠接受同种异体角膜移植术后，局部给予激素，6只正常大鼠作为正常对照组，用裂隙灯显微镜观察角膜透明性和新生血管形成情况。术后第5天取角膜进行组织病理学检查，采用实时荧光定量PCR（real-time PCR，RT-PCR）检测移植角膜TLR 2、TLR 3、TLR 4 mRNA的表达，结果同种异体移植组和激素组大鼠移植物增厚，新生血管生长，无排斥反应发生直到术后第9天才出现移植物排斥反应，而同种异体移植组在第7天就出现了移植物排斥反应，表现为角膜水肿、浑浊和新生血管形成，同种异体移植组移植物结构紊乱，排斥移植物中可见大量炎症细胞，同种异体移植组移植物中TLR 2 mRNA的表达明显高于激素组，激素组移植物中TLR 2 mRNA的表达明显高于同种异体移植组。术后9天较术后5-7天明显升高组间比较，各组在不同时间点的变化有显著性差异（P0.05）TLR 3 mRNA表达在三组间差异有统计学意义（P0.05（F= 15.35，P =0.00）及各时间点（F=4.86，TLR 3 mRNA在不同时间的表达差异无统计学意义TLR 4 mRNA表达在各组间差异有统计学意义（P0.05（F= 19.71，P =0.00）及各时间点（F= 4.14，P =0.03）结论作为天然免疫系统的识别受体，TLR 2 mRNA在排斥反应中的过度表达可能与移植物对外源性抗原的识别有关，这可能与穿透性角膜移植术后的急性排斥反应有关。
BackgroundToll-like receptors(TLRs)can initiate the nature immunity and further induce the acquired immunity.However,whether TLRs can recognize foreign to mediate the immunity rejection following the organ or tissue transplantation is seldom reported.ObjectiveThe present study was to explore the role of TLR2,TLR3 and TLR4 in graft rejection following penetrating keratoplasty.MethodsOne hundred and eight SPF female SD rats were as receipts,and 36 SPF Wistar rats served as donors in this study.The homograft of cornea was performed on 36 receipts rats.Allografts of cornea were curried out in 72 receipts,and hormone was topically administered in 36 receipts undergone allograft rats.The another 6 matched normal rats served as normal control group.The transparency and neovascularization of cornea were examined by slit-lamp microscope and the rejection index of graft was calculated based on the inflammatory score of graft.Corneas were exsected for histopathological examination,and real-time PCR(RT-PCR)was employed to determine the expressions of TLR2,TLR3 and TLR4 mRNA in grafts in the fifth day,the seventh day and the ninth day after operation.The usage of animals followed the Statement of ARVO.ResultsThe thickness of graft and growth of new blood vessel were seen in the rats of homograft group and hormone group but no rejection occurred till the ninth day after operation.However,in allograft group,the graft rejection appeared in the seventh day,showing the edema,opacity and neovascularization of cornea.The structural disorder of graft and a lots of inflammatory cells were seen in the rejected grafts in allograft group,and mild inflammatory reaction was found in the grafts of homograft group and hormone group.The expressions of TLR2 mRNA in the grafts of allograft group were significantly higher in 9 days compared with 5-7 days after operation(P0.05).The intergroup comparison showed the evidently changes in different groups in various time points(P0.05),but obviously difference was exhibited in the expression of TLR3 mRNA among the three groups(F=15.35,P=0.00)and various time points(F=4.86,P=0.02).No significant differences were found in the expression of TLR3 mRNA in different time(P0.05).There were statistically significant differences in the expression of TLR4 mRNA among groups(F=19.71,P=0.00)and various time points(F=4.14,P=0.03).ConclusionAs the recognized receptors of native immune system,the overexpression of TLR2 mRNA in the rejected graft may recognize foreign antigen.This procedure is related to acute graft rejection after penetrating keratoplasty.