中期因子调控巨噬细胞活化在肾间质纤维化中的作用

Role of midkine in regulating macrophage activation in renal interstitial fibrosis

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。

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.