IL-17C影响小鼠移植肾存活的机制  

Mechanism of effect of IL-17C on survival of kidney graft in mice

作　　者：崔瀚文 张颖[1] 孙致强 李聪然 金海龙 李响 蔡明 袁清 Cui Hanwen;Zhang Ying;Sun Zhiqiang;Li Congran;Jin Hailong;Li Xiang;Cai Ming;Yuan Qing(Department of Urology,the Fifth Center Hospital of Tianjin,Tianjin 300450,China)

机构地区：[1]天津市第五中心医院泌尿外科,300450 [2]解放军第八医学中心泌尿外科

出　　处：《器官移植》2020年第1期60-65,共6页Organ Transplantation

基　　金：国家自然科学基金项目（81570679、81200547）;北京市科技新星计划（Z161100004916141）;天津市滨海新区联合攻关项目（2014BWKL003）

摘　　要：目的探讨白细胞介素(IL)-17C在小鼠肾移植中的作用及其机制。方法以Balb/c(H-2K^d)小鼠为供体,IL-17C基因敲除(IL-17CKO)小鼠(敲除组)、C57BL/6J(H-2K^b)小鼠(野生组)为受体,建立小鼠生命支持型肾移植模型。术后比较两组小鼠的体质量及存活时间。采用苏木素-伊红(HE)染色及过碘酸-雪夫(PAS)染色对移植肾进行病理学检查。采用逆转录聚合酶链反应(RT-PCR)检测移植肾组织中颗粒酶B、干扰素(IFN)-γ、肿瘤坏死因子(TNF)-α、IL-6及IL-1β的信使核糖核酸(mRNA)表达水平,采用流式细胞术检测移植肾组织中炎症细胞浸润情况。结果移植术后敲除组小鼠存活时间显著短于野生组小鼠(P=0.031),且体质量下降程度更明显,但差异无统计学意义。病理分析发现敲除组小鼠移植肾损伤较野生组小鼠明显加重。敲除组小鼠移植肾组织中颗粒酶B、IFN-γ、TNF-α、IL-6的mRNA表达水平均显著高于野生组(均为P<0.01),IL-1βmRNA表达呈降低趋势,但差异无统计学意义(P=0.16)。流式细胞分析发现敲除组小鼠移植肾组织中CD45^+CD11b^+Ly6G^+中性粒细胞和CD45^+CD11b^+Ly6C^hi单核细胞浸润较野生组小鼠明显增加(分别为P<0.05,P<0.01),而CD45^+Ly6C^hi F4/80^+巨噬细胞浸润无明显变化(P>0.05)。结论IL-17C参与肾移植后炎症反应的调控,可能通过降低促炎细胞因子的表达及炎症细胞的浸润来减轻急性排斥反应,改善移植肾存活情况。Objective To investigate the effect and mechanism of interleukin(IL)-17C in mice undergoing kidney transplantation.Methods The life-supporting kidney transplantation mice models were established using Balb/c(H-2K^d)mice as the donors,IL-17C gene knock out(IL-17CKO)mice(knockout group)and C57BL/6J(H-2K^b)mice(wild group)were chosen as the recipients.The postoperative body mass and survival time of mice were statistically compared between two groups.Pathological examination of the kidney graft was performed by using hematoxylineosin(HE)staining and periodic acid-Schiff(PAS)staining.The expression levels of granzyme B,interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-6 and IL-1βmessenger ribonucleic acid(mRNA)in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction(RT-PCR).The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry.Results In the knockout group,the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice(P=0.031).The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group.Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group.The mRNA expression levels of granzyme B,IFN-γ,TNF-α,IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group(all P<0.01).The mRNA expression level of IL-1βshowed a decreasing trend with no statistical significance(P=0.16).Flow cytometry analysis revealed that the infiltration of CD45^+CD11b^+Ly6G^+neutrophil and CD45^+CD11b^+Ly6C^hi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice(P<0.05,P<0.01),whereas the infiltration of CD45^+Ly6C^hiF4/80^+macrophage did not significantly differ between two groups(P>0.05).Conclusions IL-17C participates in the regulation of inflammatory respon

关 键 词：白细胞介素-17C 肾移植 移植物存活 促炎细胞因子 急性排斥反应 炎症细胞浸润 

分 类 号：R617[医药卫生—外科学] R392.4[医药卫生—临床医学]