INTRODUCTION Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. AIM To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. RESULTS The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1β, IL-6, IL-10, TNF-α, TGF-β, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis. CONCLUSION Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.

中文翻译：

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P2Y6受体抑制作用通过减少小胶质细胞吞噬作用加剧了缺血性脑损伤。

简介清除受损细胞和碎片对于缺血性脑损伤后的功能恢复是有益的。但是，缺血性中风后介导小胶质细胞吞噬作用的特定吞噬受体尚不清楚。目的探讨P2Y6受体介导的小胶质细胞吞噬作用是否对缺血性中风后的碎片清除和功能恢复有利。结果短暂脑中动脉闭塞后3天内小胶质细胞P2Y6受体表达增加。选择性抑制剂MRS2578抑制小胶质细胞吞噬作用可增加缺血性中风后的脑萎缩和水肿体积，随后通过改良的神经系统严重程度评分和Grid Walk测试来衡量神经功能的恶化。MRS2578处理对IL-1α，IL-1β的表达无影响，缺血性中风后的IL-6，IL-10，TNF-α，TGF-β和MPO。最后，我们发现缺血小鼠大脑中的小胶质细胞吞噬作用抑制后，肌球蛋白轻链激酶的表达降低，这表明肌球蛋白轻链激酶参与了P2Y6受体介导的吞噬作用。结论我们的结果表明P2Y6受体介导的小胶质细胞吞噬作用在缺血性中风的急性期起着有益的作用，它可以作为缺血性中风的治疗靶标。