Department of ICU, Yancheng City No. 1 People's Hospital, Yancheng, China.
Nursing College of Nantong University, Nantong, China.
Shock. 2018 Aug;50(2):233-239. doi: 10.1097/SHK.0000000000001006.
Sepsis is a major cause of acute kidney injury (AKI), with high rates of morbidity and mortality. M2 macrophages have been shown to play important roles in the secretion of anti-inflammatory and tissue repair mediators. In this study, we investigate the role of M2 macrophages in sepsis-induced AKI by depleting these cells in vivo through the systemic administration of liposomal clodronate (LC).
Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham surgery. Biochemical and histological renal damage was assessed. Macrophage infiltration and M2 macrophage depletion were assessed by immunohistochemistry. RT-PCR was used to investigate the expression of the inducible nitric oxide synthase (iNOS), arginase 1 (Arg-1), and found in inflammatory zone 1 (FIZZ1) mRNAs. Western blots were performed to assay the tissue levels of interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α).
M2 macrophages were obviously detected 72 h after sepsis-induced AKI. Kidney injury was more severe, renal function was decreased, and blood creatinine and blood urea nitrogen (BUN) levels were higher after M2 macrophage depletion. M2 macrophage depletion significantly inhibited the proliferation of tubular cells. M2 macrophage depletion also downregulated IL-10 expression and increased TNF-α secretion during sepsis-induced AKI.
M2 macrophages attenuate sepsis-induced AKI, presumably by upregulating IL-10 expression and suppressing TNF-α secretion.
脓毒症是急性肾损伤（AKI）的主要原因，其发病率和死亡率都很高。M2 巨噬细胞已被证明在抗炎和组织修复介质的分泌中发挥重要作用。在这项研究中，我们通过全身给予脂质体氯膦酸盐（LC）来耗尽体内的 M2 巨噬细胞，从而研究 M2 巨噬细胞在脓毒症诱导的 AKI 中的作用。
雄性 Sprague-Dawley 大鼠接受盲肠结扎和穿刺（CLP）或假手术。评估生化和组织学肾损伤。通过免疫组织化学评估巨噬细胞浸润和 M2 巨噬细胞耗竭。使用 RT-PCR 研究诱导型一氧化氮合酶（iNOS）、精氨酸酶 1（Arg-1）和炎症区 1（FIZZ1）mRNA 的表达。进行 Western blot 以检测组织中白细胞介素 10（IL-10）和肿瘤坏死因子 alpha（TNF-α）的水平。
M2 巨噬细胞在脓毒症诱导的 AKI 后 72 小时明显被检测到。M2 巨噬细胞耗竭后，肾损伤更严重，肾功能下降，血肌酐和血尿素氮（BUN）水平升高。M2 巨噬细胞耗竭明显抑制了肾小管细胞的增殖。M2 巨噬细胞耗竭还下调了脓毒症诱导的 AKI 期间的 IL-10 表达并增加了 TNF-α的分泌。
M2 巨噬细胞减轻脓毒症诱导的 AKI，可能是通过上调 IL-10 表达和抑制 TNF-α 分泌。
