MIF依赖性巨噬细胞在顺铂诱导的急性肾损伤中的作用

目的探讨巨噬细胞迁移抑制因子(MIF)依赖性巨噬细胞在顺铂诱导的急性肾损伤(AKI)中的作用和机制。方法 MIF基因敲除(MIF^-/-)小鼠被随机分为正常对照组(n=6)和实验组(n=18)。正常对照组小鼠尾静脉注射生理盐水,实验组小鼠腹腔注射顺铂建立AKI模型。建模6 h后小鼠被随机分为AKI模型组、巨噬细胞对照组和MIF^-/-巨噬细胞组(每组n=6),尾静脉分别注射生理盐水、野生型C57BL/6J小鼠的巨噬细胞、MIF^-/-小鼠的巨噬细胞。3 d后处死小鼠,收集血清和肾脏组织标本。评估肾功能、肾组织病理学改变以及肾组织中单核细胞趋化蛋白(MCP-1)和TNF-α的分布与表达,检测肾组织中Mincle、诱导型一氧化氮合酶(iNOS)、F4/80的蛋白表达。结果与AKI模型组相比,巨噬细胞对照组小鼠血清肌酐升高(P <0.001)、肾小管坏死加重(P <0.001),肾脏中MCP-1和TNF-α的蛋白表达增加(P均<0.01),M1型巨噬细胞增多(P <0.001)。与巨噬细胞对照组相比,MIF<...

The role of MIF-dependent macrophages in cisplatin induced acute kidney injury

Objective To investigate the role and mechanism of macrophage migration inhibitor (MIF)-dependent macrophages in cisplatin-induced acute kidney injury （AKI）. Methods MIF gene knockout male mice were randomly divided into the normal control group （n = 6） and experimental group （n = 18）. Mice in the normal control group were injected with saline via the tail vein. In the experimental group, the AKI mouse models were established by intraperitoneal injection of cisplatin. At 6 h after AKI model establishment, the mice were randomly divided into the AKI model group, macrophage control group, and MIF^-/- macrophage group （n = 6 in each group）, which were injected with saline, macrophages from C57BL/6J mice and macrophages from MIF^-/- mice through the tail vein, respectively. After 3-d feeding, the blood and renal tissue samples were collected. The renal function, pathological changes of renal tissues, the localization and expression of monocyte chemoattractant protein-1 （MCP-1） and tumor necrosis factor-α （TNF-α） were evaluated. The expression levels of Mincle, inducible nitric oxide synthase （iNOS） and F4/80 proteins in the kidney were quantitatively detected. Results Compared with the AKI model group, the serum level of creatinine was significantly up-regulated （P < 0.001）, the renal tubular necrosis was significantly aggravated （P < 0.001）, the expression levels of MCP-1 and TNF-α proteins in the kidney were remarkably up-regulated （both P < 0.01), and the ratio of M1 macrophages was significantly increased （P < 0.001） in the macrophage control group. Compared with the macrophage control group, the serum level of creatinine was significantly down-regulated （P < 0.001）, the renal tubular necrosis was considerably alleviated （P < 0.001）, the expression levels of MCP-1and TNF-α proteins in the kidney were remarkably down-regulated （both P < 0.01）, and the ratio of M1 macrophages was significantly decreased （P < 0.001） in the MIF^-/- macrophage group. Conclusion During the process of cisplatin-induced AKI, MIF promotes the activation of macrophages and increases the production of inflammatory cytokines by activating Mincle, which exacerbates the renal inflammatory injury.