目的 观察氧连接N-乙酰葡萄糖胺（O-linked N-acetylglucosamine，O-GlcNAc）水解酶抑制剂MK8719在脑缺血损伤大鼠中的作用。 方法 建立大鼠大脑中动脉梗塞模型模拟脑缺血再灌注损伤，通过2，3，5-三苯基氯化四氮唑（2，3，5-Triphenyltetrazolium chloride，TTC）染色评估脑梗死体积，并通过改良的神经损伤评分量表评估大鼠的神经运动障碍减轻，HE和尼式染色用于评估脑损伤后组织改变，组织免疫荧光染色用于评估抗炎型小胶质细胞活化情况。体外培养BV2小胶质细胞并建立氧糖剥夺/复糖复氧模型模拟缺血缺氧再灌注损伤，Western blotting检测总蛋白及核蛋白中的信号转导及转录激活蛋白6（signal transducer and activator of transcription 6，STAT6）、磷酸化STAT6及O-GlcNAc糖基化STAT6表达。酶联免疫吸附检测（Enzyme linked immunosorbent assay，ELISA）评估小胶质细胞释放的炎性因子白细胞介素-6（interleukin-6，IL-6）、白细胞介素-1β（interleukin-1β，IL-1β）、白细胞介素-10（interleukin-10，IL-10）和转化生长因子-β（transforming growth factor-β，TGF-β）量。 结果 MK8719给药组大鼠梗死灶体积减小，神经运动障碍，抗炎型小胶质细胞比例增加；在体外培养的小胶质细胞中，MK8719组的O-GlcNAc糖基化STAT6、磷酸化STAT6及核STAT6表达增加（P<0.001），促炎因子（IL-6及IL-1β）释放减少（P<0.001），抗炎因子（IL-10及TGF-β）释放增加（P<0.001）。 结论 MK8719对脑缺血损伤大鼠有保护作用，其作用机制可能与STAT6激活诱导的抗炎型小胶质细胞活化有关。

Objective To investigate the effects of MK8719 （an inhibitor of O-linked N-acetylglucosamine［O-GlcNAc］ hydrolase） in a rat model of cerebral ischemic injury. Methods A rat middle cerebral artery occlusion model was established to simulate cerebral ischemia/reperfusion injury. We assessed cerebral infarct volume with 2，3，5-triphenyltetrazolium chloride staining；evaluated neuromotor function using the modified Neurological Severity Score；observed cerebral tissue changes after injury with Nissl staining and HE staining；and assessed the activation of anti-inflammatory microglia by immunofluorescence assay. An in-vitro BV2 microglia-based oxygen and glucose deprivation/re-oxygenation model was established to simulate ischemia-hypoxia/reperfusion injury. We measured the levels of total signal transducer and activator of transcription 6（STAT6），nuclear STAT6，phosphorylated STAT6，and O-GlcNAcylated STAT6 by Western blot；and measured the levels of pro-inflammatory interleukin（IL）-6 and IL-1β and anti-inflammatory IL-10 and transforming growth factor-β（TGF-β） released from microglia by enzyme-linked immunosorbent assay. Results The model rats treated with MK8719 showed a significantly smaller cerebral infarct size，significantly alleviated neurological deficits，and a significantly higher proportion of anti-inflammatory microglia. BV2 cells treated with MK8719 showed significantly increased expression of O-GlcNAcylated STAT6，phosphorylated STAT6（P<0.001），and nuclear STAT6，significantly reduced release of IL-6 and IL-1β（P<0.001），and significantly increased release of IL-10 and TGF-β（P<0.001）. Conclusion MK8719 can produce neuroprotective effects in rats with cerebral ischemic injury，which may be mediated by STAT6 activating anti-inflammatory microglia.