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首页> 外文期刊>Journal of Neuropathology and Experimental Neurology: Official Journal of the American Association of Neuropathologists, Inc >Neuroprotective Effects of Gabapentin Against Cerebral Ischemia Reperfusion-Induced Neuronal Autophagic Injury via Regulation of the PI3K/Akt/mTOR Signaling Pathways
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Neuroprotective Effects of Gabapentin Against Cerebral Ischemia Reperfusion-Induced Neuronal Autophagic Injury via Regulation of the PI3K/Akt/mTOR Signaling Pathways

机译：加布普坦肝素对脑缺血再灌注诱导神经元自噬损伤的神经保护作用通过调节PI3K / AKT / MTOR信号传导途径

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摘要

Gabapentin (GBP), an analgesic, adjunct antiepileptic, and migraine prophylactic drug, reduces neuronal injury induced by cerebral ischemia reperfusion (IR). However, the underlying biological molecular mechanism of GBP neuroprotection is not clear. In this study, we confirmed that dose-dependent (75 and 150mg/kg) GBP treatment could significantly reduce IR-induced neuronal death. IR-induced neuronal death was inhibited by pretreatment with 150mg/kg GBP in a middle cerebral artery occlusion rat model. In addition, 150mg/kg GBP treatment remarkably promoted the levels of antioxidants and reduced the autophagy of neurons in the infarct penumbra. Moreover, the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway was activated by pretreatment with 150mg/kg GBP, as detected by Western blot analyses. In vitro, pretreatment of PC12 cells with 450 mu M GBP significantly reduced cell death induced by oxygen-glucose deprivation, increased antioxidant function, and reduced the levels of autophagy and reactive oxygen species via activation of the PI3K/Akt/mTOR pathway. This neuroprotection by GBP was inhibited significantly by 10 mu M LY294002. In summary, dose-dependent pretreatment with GBP protected against cerebral IR injury via activation of the PI3K/Akt/mTOR pathway, which provided a neuroprotective function to inhibit oxidative stress-related neuronal autophagy.
机译：加巴亨坦（GBP），镇痛药，辅助抗癫痫和偏头痛预防药物，减少了脑缺血再灌注（IR）诱导的神经元损伤。然而，GBP神经保护的潜在生物分子机制尚不清楚。在这项研究中，我们证实，剂量依赖性（75和150mg / kg）GBP处理可显着降低IR诱导的神经元死亡。通过在中部脑动脉闭塞大鼠模型中用150mg / kg GBP进行预处理来抑制IR诱导的神经元死亡。此外，150mg / kg GBP治疗显着促进了抗氧化剂水平，并减少了梗塞半影中神经元的自噬。此外，通过蛋白质印迹分析检测，通过用150mg / kg GBP预处理来激活磷酸阳性-3-激酶（PI3K）/蛋白激酶B（akt）/哺乳动物靶标在150mg / kg GBP。体外，用450μm的PC12细胞预处理，具有450μm的GBP，显着降低了通过氧 - 葡萄糖剥夺，抗氧化功能增加的细胞死亡，并通过激活PI3K / AKT / mTOR途径降低了自噬和活性氧物种的水平。通过10μmL294002显着抑制了GBP的这种神经保护。总之，通过激活PI3K / AKT / MTOR途径，通过激活脑IR损伤的GBP进行剂量依赖性预处理，该方法提供了神经保护功能来抑制氧化应激相关的神经元自噬。

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