补体C5a受体1拮抗剂对小鼠上行性泌尿道感染的保护作用  

Protective effect of C5a receptor 1 antagonist on ascending urinary tract infection in mice

作　　者：张婷[1] 武坤毅 王娜[1] 宋云[1] 赵国秀 赵璇 李可[1] Zhang Ting;Wu Kunyi;Wang Na;Song Yun;Zhao Guoxiu;Zhao Xuan;Li Ke(Core Research Laboratory,the Second Affiliated Hospital,Xi＇an Jiaotong University,Xi＇an 710004,China)

机构地区：[1]西安交通大学第二附属医院科研中心实验室,710004

出　　处：《中华肾脏病杂志》2018年第6期439-445,共7页Chinese Journal of Nephrology

基　　金：国家自然科学基金(81170644、81770696)

摘　　要：目的探讨补体C5a受体1（C5aR1）拈抗剂对小鼠上行性泌尿道感染的保护作用。方法（1）雌性C57BL／6小鼠被随机分为实验组与对照组，每组各38只，采用尿道插管推注大肠杆菌（E．coli）法制作上行性泌尿道感染模型。实验组于造模前2h或造模后3h给予腹腔注射C5aR1拮抗剂（W54011或PMX53）；对照组给予生理盐水或多肽。分别于感染后24h、48h评估小鼠膀胱和肾脏感染情况：平板涂布法检测膀胱及肾组织细菌量；实时定量PCR法检测肾脏各炎性因子mRNA的表达；HE染色检查肾组织炎性细胞浸润及损伤程度。（2）原代培养肾小管上皮细胞，随机分为拮抗剂组和对照组，细胞实验检测和比较两组肾小管上皮细胞的细菌黏附量。结果与对照组相比，造模前给予C5aR1拮抗剂的W54011亚组和PMX53亚组小鼠，感染后48h膀胱和肾组织细菌量降低（均P〈0．01）；W54011亚组小鼠肾组织病理评分降低（均P〈0．05）；感染后24h肾脏炎性因子，包括：趋化因子（C-X-C序列）配体1（CXCL-1）、白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）的mRNA表达降低（均P〈0．05）。与对照组相比，造模后给予C5aR1拮抗剂的PMX53亚组小鼠，感染后48h膀胱和肾组织细菌量降低（均P〈0．01）。细胞实验结果显示，与对照组比较，W54011组和PMX53组黏附于细胞上的细菌量减少（均P〈0．05）。结论C5aR1拈抗剂可改善泌尿道感染组织病理改变，减轻。肾脏炎性反应和减少黏附于肾小管上皮的细菌量。C5aR1可能成为预防及治疗泌尿道感染的有效靶点。Objective To investigate the protective effect of complement 5a receptor 1 （C5aR1） antagonist on ascending urinary tract infection in mice. Methods （1） Female C57BL/6 mice were randomly divided into experimental and control groups： 38 mice in each group, and inoculated with E. coli by urethral catheterization to set up the ascending urinary tract infection model. C5aR1 antagonist （W54011 or PMX53） and corresponding control （PBS or control peptide） were initially given either at 2 h before or 3 h after infection by intraperitoneal injection. Mice were sacrificed to assess the infection in bladder and kidney at 24 or 48 h after infection. The bacterial load of bladder and kidney tissue was measured by agar plate assay. The mRNA expression of renal inflammatory factors was detected by realtime RCR. The renal tissue injury and inflammatory cell infiltration were assessed by HE staining and pathological scores. （2） Primary cuhured renal tubular epithelial cells were randomly divided into antagonist and control groups to detect and compare the bacterial adhesion to renal tubular epithelial cells in vitro. Results Compared with control groups, the initial delivery of C5aR1 antagonist （W54011 or PMX53） before E.coli inoculation reduced the bacterial load in bladder and kidney tissue 48 h after infection （all P 〈 0.01）. In experimental group given W54011 before infection, the renal pathological scores were reduced （both P 〈 0.05）, as well as renal inflammatory factor expressions： CXCL-1 mRNA, IL-6 mRNA and TNF-α mRNA （all P 〈 0.05）. Compared with corresponding control groups, the initial delivery of PMX53 after E. coli inoculation could also reduce the bacterial load in bladder and kidney tissue 48 h after infection （both P 〈 0.01）. Furthermore, C5aR1 antagonists W54011 and PMX53 could decrease bacteria adhesion to renal tubular epithelial cells in vitro, compared with control groups （both P 〈 0.05）. Conclusions C5aR1 antagonists can significantly attenuate renal

关 键 词：泌尿道感染 补体C5A 上皮细胞 肾小管 C5a受体1拮抗剂 

分 类 号：R691.3[医药卫生—泌尿科学]