Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits afer hypoxiaischemia-induced brain damage in newborn rats
Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits afer hypoxiaischemia-induced brain damage in newborn rats
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自噬抑制对新生大鼠缺氧缺血脑损伤后海马谷氨酸受体亚基的神经保护作用
DOI：
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Xing Feng
中科院分区：
文献类型：
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作者：
Li-xiao Xu;Xiao-juan Tang;Yuan-yuan Yang;Mei Li;Mei-fang Jin;Po Miao;Xin Ding;Ying Wang;Yan-hong Li;Bin Sun;Xing Feng
自噬参与了缺氧缺血性脑损伤(HIBD)的病理过程。然而，它在HIBD中的调控作用仍不清楚，因此在这里使用了一个大鼠模型进行了研究。结扎新生大鼠左颈总动脉造成HIBD，低氧2小时。部分大鼠在动脉结扎前1小时给予自噬抑制剂3-甲基腺嘌呤(10μL，10 mM)或自噬刺激剂雷帕霉素(1g/kg)。我们的研究结果表明，新生大鼠缺氧缺血所致的海马损伤伴随着自噬相关蛋白轻链3和Beclin-1以及AMPA受体亚单位GluR1的表达增加，而GluR2的表达降低。用自噬抑制剂3-甲基腺嘌呤预处理可阻断缺氧缺血所致的海马区损伤，而用自噬刺激剂雷帕霉素预处理则显著加重海马区的损伤。此外，3-甲基腺嘌呤可阻断缺氧缺血诱导的GluR1表达上调和GluR2表达下调。相比之下，雷帕霉素进一步提高了HIBD新生儿海马区GluR1的水平，并加剧了GluR2表达的下降。我们的结果表明，抑制自噬有助于预防新生大鼠的HIBD，至少在一定程度上是通过正常化GluR1和GluR2的表达。
Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage (HIBD). However, its regulatory role.in HIBD remains unclear and was thus examined here using a rat model. To induce HIBD, the lef common carotid artery was ligated in.neonatal rats, and the rats were subjected to hypoxia for 2 hours. Some of these rats were intraperitoneally pretreated with the autophagy.inhibitor 3-methyladenine (10 mM in 10 μL) or the autophagy stimulator rapamycin (1 g/kg) 1 hour before artery ligation. Our fndings.demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the.autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR1, but by reduced expression of GluR2..Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury, whereas pretreatment.with the autophagy stimulator rapamycin signifcantly augmented hippocampal injury. Additionally, 3-methyladenine pretreatment blocked.the hypoxia-ischemia-induced upregulation of GluR1 and downregulation of GluR2 in the hippocampus. By contrast, rapamycin further.elevated hippocampal GluR1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD. Our results indicate that.autophagy inhibition favors the prevention of HIBD in neonatal rats, at least in part, through normalizing GluR1 and GluR2 expression.