摘要： 目的 探讨中期因子（MK）调控巨噬细胞活化在肾间质纤维化（RIF）中的作用。方法 通过单侧输尿管结扎（UUO）建立小鼠RIF模型。将小鼠分为假手术组、UUO 7 d组、UUO 14 d组，通过Masson染色、流式细胞术、实时荧光定量PCR和体外细胞培养技术检测各组小鼠受损肾脏胶原纤维沉积、巨噬细胞变化情况以及MK、炎性细胞因子、精氨酸酶-1（Arg-1）的变化情况。结果 纤维化的肾组织中MK表达显著上调。小鼠RIF模型的肾组织中巨噬细胞数量增多，炎性细胞因子白细胞介素-1b（IL-1b）、IL-6、IL-4和Arg-1 mRNA表达水平升高。体外研究显示，MK显著促进RAW264.7巨噬细胞中IL-6 mRNA表达水平升高，但IL-1b、IL-4和Arg-1 mRNA表达水平未升高。结论 靶向阻断MK可抑制M1样巨噬细胞的活化，改善RIF程度，进而抑制慢性肾脏病的进程。

中期因子调控巨噬细胞活化在肾间质纤维化中的作用

罗钢¹, 祝雪妍¹, 朱迪²

1. 辽宁省妇幼保健院儿科, 沈阳 110005;
2. 中国医科大学附属第一医院儿科, 沈阳 110001

收稿日期:2021-07-16出版日期:2022-01-30发布日期:2021-12-30
通讯作者:罗钢E-mail:syluogang@sina.com
作者简介:罗钢(1972-),男,副主任医师,博士.
基金资助:辽宁省大型科学仪器设备共享服务平台能力建设项目（LNDY-20170014）


关键词: 肾间质纤维化, 中期因子, 巨噬细胞
Abstract: Objective To investigate the role of midkine (MK) in regulating macrophage activation in renal interstitial fibrosis (RIF). Methods A murine model of RIF was established by inducing unilateral ureteral obstruction (UUO). Masson staining, flow cytometry, real time-polymerase chain reaction, and in vitro cell culture were performed to detect collagen deposition and changes in macrophages, MK, inflammatory cytokines, and arginine-1 (Arg-1). Results The expression of MK in the fibrotic kidney tissue was significantly increased, accompanied by an increased number of macrophages in the interstitial fibrosis tissue of the mice model of RIF. Activated macrophages expressed a variety of inflammatory cytokines, including interleukin-1b (IL-1b), IL-6, IL-4, and Arg-1 mRNA. In vitro studies showed that MK significantly promoted the expression of IL-6 mRNA in lipopolysaccharide-stimulated RAW264.7 cells, but did not significantly alter the expression of IL-6, IL-4, and Arg-1 mRNA. Conclusion Blocking MK may inhibit the activation of M1 macrophages and improve the degree of RIF, thus preventing the progression of chronic kidney disease.
Key words: renal interstitial fibrosis, midkine, macrophage
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