Aim. The protection against ischemia/reperfusion injury mediated by remote limb ischemic postconditioning (RIPC) shows great clinical value in ischemic stroke therapy, but the particular mechanism of RIPC remains unclear. Methods. We carried out middle cerebral artery occlusion/reperfusion (MCAO/R) surgery on C57BL/6 male mice. RIPC was generated by 10-minute occlusion followed by the same period of reperfusion of the bilateral hind limb femoral artery and repeated for 3 cycles. Infarct size and neurological score were performed to assess stroke outcomes. Ly6C^hi monocytes were quantified in the blood and brain by flow cytometry. Real-time PCR, ELISA, and immunofluorescence were utilized to detect phenotype of proinflammatory M1 and anti-inflammatory M2 microglia/macrophage. Nuclear factor κB (NF-κB) and peroxisome proliferator-activated receptor γ (PPARγ) levels were detected using Western blot. Results. At 24 and 72 h after MCAO, RIPC drastically attenuated infarct size and ameliorated the neurological deficits of mice and facilitated transmigration of Ly6C^hi monocytes to the brain postischemia reperfusion. Furthermore, RIPC contributed to increased M2 and reduced M1 microglia/macrophage through inhibiting NF-κB and promoting PPARγ activation. Conclusion. Our results reveal pharmacological effect of RIPC in promoting microglia/macrophage transferring from M1 to M2 phenotype after MCAO/R in mice, which provides theoretical support for the therapeutic effect of RIPC in ischemic stroke.

中文翻译：

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远程肢体缺血后处理通过调节小鼠小胶质细胞/巨噬细胞极化来预防缺血性中风

瞄准。远程肢体缺血后处理（RIPC）介导的缺血/再灌注损伤保护在缺血性卒中治疗中具有重要的临床价值，但RIPC的具体机制尚不清楚。方法。我们对 C57BL/6 雄性小鼠进行了大脑中动脉闭塞/再灌注 (MCAO/R) 手术。RIPC 是通过 10 分钟的闭塞产生的，然后是双侧后肢股动脉的相同时期的再灌注，并重复 3 个周期。进行梗死面积和神经系统评分以评估卒中结局。Ly6C^嗨通过流式细胞术对血液和脑中的单核细胞进行定量。实时 PCR、ELISA 和免疫荧光用于检测促炎 M1 和抗炎 M2 小胶质细胞/巨噬细胞的表型。使用蛋白质印迹检测核因子κ B (NF- κ B) 和过氧化物酶体增殖物激活受体γ (PPAR γ ) 水平。结果。在 MCAO 后 24 和 72 小时，RIPC 显着减小了梗死面积并改善了小鼠的神经功能缺损，并促进了 Ly6C ^hi单核细胞向脑缺血后再灌注的迁移。此外，RIPC 通过抑制 NF- κ导致 M2 增加和 M1 小胶质细胞/巨噬细胞减少B 并促进 PPAR γ活化。结论。我们的研究结果揭示了RIPC促进小鼠MCAO/R后小胶质细胞/巨噬细胞从M1表型向M2表型转移的药理作用，为RIPC在缺血性脑卒中的治疗作用提供了理论支持。