白细胞介素17及趋化因子受体4在慢性移植物肾病大鼠模型中的作用  

The roles of IL-17 and CXCR4 in chronic allograft nephropathy in rat models

作　　者：王伟[1] 徐岳[1] 焦文娇 曾嵩[1] 范博涵 尹航[1] 胡小鹏[1] 张小东[1] 

机构地区：[1]首都医科大学附属北京朝阳医院泌尿外科,北京100020

出　　处：《中华医学杂志》2018年第5期370-373,共4页National Medical Journal of China

基　　金：移植耐受与器官保护北京市重点实验室开放课题（2015YZN502）

摘　　要：目的对大鼠慢性移植物肾病（CAN）模型中白细胞介素17（IL－17）及趋化因子受体4（CXCR4）的作用机制进行初步探索。方法以Fisher344大鼠为供体，Lewis大鼠为受体，制备慢性移植物肾病模型。对照组（n＝10）Lewis大鼠行同系肾移植术；实验组（n＝10）Fisher344大鼠为供体，Lewis大鼠为受体。实验组及对照组均于术后第6周处死进行取材，肾脏进行病理检查，评价移植肾损伤情况。免疫组化法及酶联免疫法检测大鼠血清及肾脏组织中基质细胞衍生因子－1/趋化因子受体4（SDF－1/CXCR4）、IL－17和α平滑肌肌动蛋白（α－SMA）水平。流式细胞仪检测CD4＋、CXCR4＋、IL－17＋细胞百分数及绝对数。结果移植后6周实验组肾脏出现明显慢性移植物肾病的病理表现。免疫组化显示SDF－1/CXCR4及IL－17在实验组的蛋白表达水平均高于对照组。实验组大鼠血液中的Th17细胞比例高于对照组[（0.19±0.05）%比（0.12±0.03）%, P〈0.05]，实验组肾脏组织中Th17细胞比例也高于对照组[（0.52±0.21）%比（0.17±0.12%），P〈0.01]。血清及肾脏组织中IL－17的蛋白表达水平，实验组[（243.12±17.63） pg/ml, （521.54±21.76） pg/ml]高于对照组[（35.78±7.34 pg/ml, 77.34±11.17 pg/ml）]，差异均有统计学意义（均P〈0.01）。结论CAN大鼠模型中Th17细胞增多，通过初步研究认为SDF－1/CXCR4的趋化作用可能使Th17聚集在受损伤的移植肾组织当中，其分泌的IL－17可能促进肾脏固有细胞向肌成纤维细胞转化，造成不可逆的肾脏损伤。ObjectiveTo investigate the role and mechanism of IL-17 and CXCR4 in chronic graft nephropathy （CAN） in rat models.MethodsCAN rat models were established using Fisher 344 to Lewis rats. In the control group（n=10）, Lewis rats were performed isotransplantation. CAN rat models were established in experimental group（n=10）. All the rats were havested 6 weeks after transplantation. Kidneys were examined by pathology to evaluate the injury of the renal allograft. SDF-1/CXCR4, IL-17 and α-SMA expression level in serum and renal graft were detected by immunohistochemical staining and Enzyme-linked immunosorbent assays（ELISA）. The percent and the absolute amount of CD4＋ cells、CXCR4＋ cells and IL-17＋ cells were detected by flow cytometry.ResultsThe graft of the experiment group showed obvious pathological features of CAN. The protein expression levels of SDF-1/CXCR4 and IL-17 in the experiment group are significantly higher than in the control group. We could also observe the number of Th17 cells has a significant increase in the experiment group[blood （0.19±0.05）% vs （0.12±0.03）%; kidney （0.52±0.21）% vs （0.17±0.12）%]. The IL-17 level also showed the same differences between the experiment[blood （243.12±17.63） pg/ml, kidney （521.54±21.76） pg/ml]and the control group[blood （35.78±7.3） pg/ml, kidney （77.34±11.1） pg/ml].ConclusionsThe Th17 cells increase in the CAN rats model, maybe the SDF-1/CXCR4 has a chemotaxis to collect Th17 cells to the injured kidney. And its expression of IL-17 may promote the renal cells to transform into fibroblasts.

关 键 词：受体CXCR4 白细胞介素17 肾移植 

分 类 号：R-332[医药卫生] R699.2