Sevoflurane post-conditioning attenuates traumatic brain injury-induced neuronal apoptosis by promoting autophagy via the PI3K/AKT signaling pathway.
Sevoflurane post-conditioning attenuates traumatic brain injury-induced neuronal apoptosis by promoting autophagy via the PI3K/AKT signaling pathway.
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DOI：
10.2147/dddt.s158313
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Fu H
中科院分区：
文献类型：
--
作者：
He H;Liu W;Zhou Y;Liu Y;Weng P;Li Y;Fu H
七氟醚后处理通过抑制创伤性脑损伤（TBI）后半胱天冬酶依赖的神经元凋亡发挥神经保护作用。内质网应激诱导的自噬在脑外伤后继发性神经功能障碍中起重要作用。然而，自噬和半胱天冬酶依赖性细胞凋亡之间的关系以及TBI后七氟烷后处理发生的潜在神经保护机制仍不清楚。Feeney TBI模型用于诱导大鼠脑损伤。采用改良神经系统严重程度评分评价、脑含水量测量、尼氏染色和末端脱氧核苷酸转移酶dUTP缺口末端标记法测定七氟烷后处理的神经保护作用。免疫荧光和Western blot分析用于检测自噬相关蛋白微管相关蛋白1轻链3-II和Beclin-1、促凋亡因子的表达，以及损伤皮质内磷脂酰肌醇3-激酶/蛋白激酶B（PI 3 K/AKT）信号通路的激活。自噬和神经元凋亡被激活损伤后的皮层TBI。七氟醚后处理可促进早期自噬，抑制神经元凋亡，减轻脑水肿，改善TBI后神经功能（均P < 0.05）。七氟醚后处理可诱导TBI后PI 3 K/AKT信号通路的激活（P < 0.05）。七氟烷后处理的神经保护作用通过自噬抑制剂3-甲基腺嘌呤治疗逆转。神经元凋亡和自噬激活参与了脑外伤后的继发性神经损伤。七氟醚后处理通过PI 3 K/AKT信号通路调节自噬，减弱TBI诱导的神经元凋亡。
Sevoflurane post-conditioning exerts nerve-protective effects through inhibiting caspase-dependent neuronal apoptosis after a traumatic brain injury (TBI). Autophagy that is induced by the endoplasmic reticulum stress plays an important role in the secondary neurological dysfunction after a TBI. However, the relationship between autophagy and caspase-dependent apoptosis as well as the underlying nerve protection mechanism that occurs with sevoflurane post-conditioning following a TBI remains unclear. The Feeney TBI model was used to induce brain injury in rats. Evaluation of the modified neurological severity scores, measurement of brain water content, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to determine the neuroprotective effects of the sevoflurane post-conditioning. Both immunofluorescence and Western blot analyses were used to detect the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3-II and Beclin-1, pro-apoptotic factors, as well as the activation of the phosphatidylinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway within the lesioned cortex. Autophagy and neuronal apoptosis were activated in the lesioned cortex following the TBI. Sevoflurane post-conditioning enhanced early autophagy, suppressed neuronal apoptosis, and alleviated brain edema, which improved nerve function after a TBI (all P < 0.05). Sevoflurane post-conditioning induced the activation of PI3K/AKT signaling after the TBI (P < 0.05). The neuroprotective effects of sevoflurane post-conditioning were reversed through the autophagy inhibitor 3-methyladenine treatment. Neuronal apoptosis and the activation of autophagy were involved in the secondary neurological injury following a TBI. Sevoflurane post-conditioning weakened the TBI-induced neuronal apoptosis by regulating autophagy via PI3K/AKT signaling.