内源代谢物烟酰胺缓解小鼠自发性狼疮肾炎的症状  

Endogenous metabolite nicotinamide alleviates spontaneous lupus nephritis progression in a mouse model

作　　者：申彦彦 刘艳红 韩秋影 李爱玲 夏晴[1] 张学敏[1] 张维娜 SHEN Yanyan;LIU Yanhong;HAN Qiuying;LI Ailing;XIA Qing;ZHANG Xuemin;ZHANG Weina(National Center for Biomedical Analysis,Beijing 100039,China)

机构地区：[1]国家生物医学分析中心,北京100039

出　　处：《军事医学》2024年第6期468-473,共6页Military Medical Sciences

基　　金：国家自然科学基金优秀青年科学基金项目(82022030)。

摘　　要：目的构建系统性红斑狼疮疾病NZB/W(F1)小鼠模型,评价内源代谢小分子烟酰胺对NZB/W(F1)模型小鼠狼疮肾炎发病过程中各指标的影响,为烟酰胺在狼疮肾炎治疗中的作用提供依据。方法通过雄性NZW小鼠与雌性NZB小鼠杂交获取雌性NZB/W(F1)小鼠,利用代谢笼收集小鼠24 h尿液样本并利用蛋白尿试纸检测小鼠蛋白尿水平;通过眼眶静脉丛获取小鼠血液样本,利用酶联免疫吸附试验(ELISA)检测血清中双链DNA抗体水平;利用全自动生化分析仪检测血清中血肌酐、尿素氮水平以及肝功能指标;通过苏木精-伊红染色和组织免疫荧光技术检测小鼠肾脏病理状态。结果雌性NZB/W(F1)小鼠在自然发病过程中蛋白尿水平逐渐升高,血清中双链DNA抗体、血肌酐和尿素氮水平随周龄逐步升高,显示NZB/W(F1)小鼠狼疮肾炎疾病模型构建成功。与对照组同周龄小鼠相比,烟酰胺饲喂能够明显缓解小鼠蛋白尿水平(P=0.0070),抑制血清中双链DNA抗体产生(P=0.0325),缓解血肌酐(P=0.0067)和尿素氮(P=0.0166)指标发展,同时烟酰胺饲喂组小鼠肾脏损伤较对照组明显减轻。结论成功构建NZB/W(F1)狼疮肾炎小鼠模型,发现烟酰胺饲喂能够明显缓解NZB/W(F1)小鼠狼疮肾炎的疾病进展。Objective To construct an NZB/W(F1)mouse model of systemic lupus erythematosus and evaluate the effects of nicotinamide on each index of lupus nephritis pathogenesis of NZB/W(F1)mice in order to provide data for research on the role of nicotinamide in the treatment of lupus nephritis.Methods Female NZB/W(F1)mice were obtained by crossing male NZW mice with female NZB ones.Urine samples were collected using metabolic cages and proteinuria test strips were used to detect proteinuria.Blood samples were collected through the orbital venous plexus in mice.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of anti-dsDNA antibody.Levels of serum creatinine and urea nitrogen and liver function indexes were detected using an automatic blood analyzer.Hematoxylin-eosin staining and immunofluorescence technique were used to detect the pathological state of the kidney.Results The levels of proteinuria,double-stranded DNA antibodies,serum creatinine,and urea nitrogen were gradually increased during the natural course of the disease in female NZB/W(F1)mice,indicating that the lupus nephritis disease model was constructed in female NZB/W(F1)mice.Compared to the control group,nicotinamide feeding could obviously decrease the level of proteinuria(P=0.0070),inhibit the production of double-stranded DNA antibodies(P=0.0325),and retard the progression of serum creatinine(P=0.0067)and urea nitrogen indexes(P=0.0166)in serum.In addition,the pathological state of the kidney in the nicotinamide feeding group was significantly alleviated compared with the control group.Conclusion A lupus nephritis disease model is constructed in NZB/W(F1)mice.Nicotinamide feeding can obviously alleviate the disease state of lupus nephritis in NZB/W(F1)mice.

关 键 词：狼疮肾炎 NZB/W(F1)小鼠 烟酰胺 动物模型 

分 类 号：R392.5[医药卫生—免疫学] R976[医药卫生—基础医学] R979.5