Department of Neurology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China.
J Immunol Res. 2021 Feb 19;2021:6688053. doi: 10.1155/2021/6688053. eCollection 2021.
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.
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 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 B (NF-B) and peroxisome proliferator-activated receptor (PPAR) levels were detected using Western blot.
At 24 and 72 h after MCAO, RIPC drastically attenuated infarct size and ameliorated the neurological deficits of mice and facilitated transmigration of Ly6C monocytes to the brain postischemia reperfusion. Furthermore, RIPC contributed to increased M2 and reduced M1 microglia/macrophage through inhibiting NF-B and promoting PPAR activation.
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.
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脑卒中治疗中具有重要的临床价值，但 RIPC 的特定机制仍不清楚。
我们对 C57BL/6 雄性小鼠进行大脑中动脉闭塞/再灌注（MCAO/R）手术。通过双侧股动脉 10 分钟闭塞后再灌注相同时间，并重复 3 个周期来实现 RIPC。通过梗塞面积和神经评分评估脑卒中结果。通过流式细胞术在血液和大脑中定量 Ly6C 单核细胞。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 Western blot 检测核因子 B（NF-B）和过氧化物酶体增殖物激活受体 （PPAR）水平。
MCAO 后 24 和 72 小时，RIPC 显著减轻了小鼠的梗塞面积和神经功能缺损，并促进了 Ly6C 单核细胞在缺血再灌注后的脑迁移。此外，RIPC 通过抑制 NF-B 和促进 PPAR 激活，促进 M2 并减少 M1 小胶质细胞/巨噬细胞。
我们的结果揭示了 RIPC 在促进 MCAO/R 后小鼠小胶质细胞/巨噬细胞从 M1 向 M2 表型转化中的药理学作用，为 RIPC 在缺血性脑卒中治疗中的疗效提供了理论支持。
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