IL-34和CSF-1在狼疮肾炎小鼠肾脏的表达及意义  

Expressions of IL-34 and CSF-1 in the Kidney of Mice with Spontaneous Lupus Nephritis

作　　者：廖文慧[1] 杜艳军[2] 曾锐[3] 

机构地区：[1]华中科技大学同济医学院附属同济医院综合科,武汉430030 [2]湖北中医药大学针灸骨伤学院,武汉430061 [3]华中科技大学同济医学院附属同济医院肾内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2015年第2期129-133,142,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81270771)

摘　　要：目的探讨巨噬细胞活化因子白细胞介素-34(IL-34)和集落刺激因子-1(CSF-1)在狼疮肾炎小鼠肾脏的表达及意义。方法以自发性狼疮肾炎小鼠MRL-Faslpr和TgZ-MRL-Faslpr小鼠为模型,于6周、3月、5月末处死动物,检测尿蛋白和血肌酐的变化;PAS染色观察肾脏病理改变;实时定量PCR和ELISA法检测肾组织IL-34和CSF-1的表达;免疫组化和免疫荧光法检测肾组织F4/80+巨噬细胞数量、雪莲花凝集素(LTL)和双花扁豆凝集素(DBA)的分布;原位杂交检测肾脏IL-34的分布;X-gal染色检测肾组织CSF-1的分布。结果 1随着鼠龄增加MRL-Faslpr小鼠肾脏IL-34和CSF-1mRNA和蛋白表达均显著增加(均P<0.01),增加的IL-34和CSF-1主要分布在皮髓交界处的肾小管中,部分分布于皮质肾小管。2肾脏IL-34和CSF-1表达增加与肾脏病理分级和肾间质巨噬细胞浸润呈量效关系。3尿蛋白定量与肾脏IL-34的表达密切相关。相关分析显示,尿IL-34含量与尿白蛋白排泌呈正相关(r=0.915 4,P<0.01),明显优于CSF-1(r=0.150 6,P=0.07)。结论与CSF-1相比,肾脏IL-34的表达和分泌与尿蛋白定量密切相关,尿IL-34含量能够反映狼疮肾炎的活动程度。Objective To investigate the expressions of interleukine-34（IL-34）and colony-stimulating factor-1（CSF-1）in the kidney of mice with spontaneous lupus nephritis and its significance. Methods MRL-Faslpr and/or TgZ-MRL-Fas^lpr mice were used to develop spontaneous lupus nephritis. Mice were sacrificed at age of 6 weeks,3 months and 6 months. Blood and urine samples were taken for detection of serum creatinine levels and urinary protein excretion, respectively. PAS staining was used to assess renal histological changes. Immunohistochemical staining was used to detect the number of F4/80- macrophage. Lotus tetragonolobus lectin（LTL）and dolichos bifows agglutinin（DBA）were detected by immunofluorescense. Real-time PCR and ELISA were used to detect the mRNA and protein expressions of IL-34 and CSF-1. The distributions of IL-34 and CSF-1 in the kidney were detected by in situ hybridization and X-gal staining, separately. Results ①The mRNA and protein levels of IL-34 and CSF-1 were increased in the kidney of MRL-Faslpr mice with the age of the mice increasing（P〈0.01）. The increased IL-34 and CSF-1 were mainly distributed in the renal tubules in the cortico-medullary junction and some in the cortical renal tubules. ②The increased levels of IL-34 and CSF-1 were associated with the pathological grades of lupus nephritis and the infiltration of macrophages in the renal interstitium. ③Proteinuria was closely correlated with the expression of IL-34（r=0. 915 4,P〈0.01）. Correlation analysis showed that urine IL-34 contents were positively associated with the excretion of urine albu- min whereas CSF-1 was weakly correlated with proteinuria（r=0. 150 6,P=0.07）. Conclusion Compared with CSF-l,renal and urine IL-34 was closely correlated with proteinuria. Urinary levels of IL-34 could reflect the severity of lupus nephritis.

关 键 词：狼疮肾炎 蛋白尿 白细胞介素-34 集落刺激因子-1 

分 类 号：R593.242[医药卫生—内科学]