DataSheet1_Riclinoctaose Attenuates Renal Ischemia-Reperfusion Injury by the Regulation of Macrophage Polarization.pdf

Renal ischemia-reperfusion injury is a major trigger of acute kidney injury and leads to permanent renal impairment, and effective therapies remain unresolved. Riclinoctaose is an immunomodulatory octasaccharide composed of glucose and galactose monomers. Here we investigated whether riclinoctaose protects against renal ischemia-reperfusion injury. In mice, pretreatment with riclinoctaose significantly improved renal function, structure, and the inflammatory response after renal ischemia-reperfusion. Flow cytometry analysis revealed that riclinoctaose inhibited ischemia-reperfusion-induced M1 macrophage polarization and facilitated M2 macrophage recruitment into the kidneys. In isolated mouse bone marrow-derived macrophages, pretreatment with riclinoctaose promoted the macrophage polarization toward M2-like phenotype. The inhibitor of Nrf-2/HO-1 brusatol diminished the effects of riclinoctaose on macrophage polarization. In mice, intravenous injection with riclinoctaose-pretreated bone marrow-derived macrophages also protected against renal ischemia-reperfusion injury. Fluorescence-labeled riclinoctaose specifically bound to the membrane of macrophages. Interfering with mDC-SIGN blocked the riclinoctaose function on M2 polarization of macrophages, consequently impairing the renoprotective effect of riclinoctaose. Our results revealed that riclinoctaose is a potential therapeutic agent in preventing renal ischemia-reperfusion injury.

肾缺血再灌注损伤（renal ischemia-reperfusion injury）是急性肾损伤的主要诱因，可引发永久性肾功能损害，目前仍未确立有效的治疗方案。Riclinoctaose是一种由葡萄糖与半乳糖单体构成的免疫调节性八糖。本研究旨在探究Riclinoctaose是否可对肾缺血再灌注损伤发挥保护作用。在小鼠模型中，经Riclinoctaose预处理可显著改善肾缺血再灌注后的肾功能、组织结构与炎症反应状态。流式细胞术（flow cytometry）分析结果显示，Riclinoctaose可抑制缺血再灌注诱导的M1型巨噬细胞极化，并促进M2型巨噬细胞向肾脏组织募集。在分离得到的小鼠骨髓源性巨噬细胞中，Riclinoctaose预处理可促使巨噬细胞向M2样表型极化。Nrf-2/HO-1通路抑制剂鸦胆子苦素（brusatol）可抵消Riclinoctaose对巨噬细胞极化的调控作用。在小鼠体内，经Riclinoctaose预处理的骨髓源性巨噬细胞经静脉注射后，同样可对肾缺血再灌注损伤起到保护作用。荧光标记的Riclinoctaose可特异性结合巨噬细胞膜表面。靶向mDC-SIGN的基因干扰可阻断Riclinoctaose调控巨噬细胞M2极化的功能，进而削弱其肾脏保护作用。本研究结果表明，Riclinoctaose是一种有望用于预防肾缺血再灌注损伤的潜在治疗制剂。