Autophagy Is Involved in the Sevoflurane Anesthesia-Induced Cognitive Dysfunction of Aged Rats.
Autophagy Is Involved in the Sevoflurane Anesthesia-Induced Cognitive Dysfunction of Aged Rats.
复制标题
自噬参与七氟烷麻醉引起的老年大鼠认知功能障碍。
DOI：
10.1371/journal.pone.0153505
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Zhang X;Zhou Y;Xu M;Chen G
自噬与神经元存活和死亡的调控有关，并与许多神经退行性疾病有关。老年患者麻醉后的术后认知功能障碍很常见，但其病理生理机制尚不清楚。在七氟醚麻醉下的老年大鼠中也发现了类似的效果；然而，自噬在七氟醚麻醉诱导的老年大鼠海马神经元凋亡中的作用尚不清楚。本研究旨在探讨自噬对七氟醚诱导的老年大鼠认知功能障碍的影响，并探讨自噬在七氟醚诱导的神经元凋亡中的作用。我们用20月龄大鼠在七氟醚麻醉下研究记忆表现、神经元凋亡和自噬。结果表明，七氟醚麻醉显著损害大鼠记忆能力，诱导海马神经元凋亡。有趣的是，雷帕霉素（一种自噬诱导剂）通过提高自噬通量，改善了七氟醚麻醉下老年大鼠的认知缺陷。雷帕霉素处理通过mTOR信号通路导致海马神经元中自噬小体和自噬溶酶体的快速积累，p62蛋白水平降低，微管相关蛋白轻链3 II （LC3-II）与LC3-I的比值升高。然而，自噬抑制剂（氯喹）的使用减弱了自噬通量，增加了七氟醚麻醉引起的神经元凋亡和记忆障碍的严重程度。这些发现提示，七氟醚麻醉后老年大鼠海马神经元自噬功能受损可能导致认知障碍。因此，我们的研究结果为七氟醚麻醉诱导的神经退行性疾病患者的自噬治疗提供了一个潜在的新靶点。
Autophagy is associated with regulation of both the survival and death of neurons, and has been linked to many neurodegenerative diseases. Postoperative cognitive dysfunction is commonly observed in elderly patients following anesthesia, but the pathophysiological mechanisms are largely unexplored. Similar effects have been found in aged rats under sevoflurane anesthesia; however, the role of autophagy in sevoflurane anesthesia-induced hippocampal neuron apoptosis of older rats remains elusive. The present study was designed to investigate the effects of autophagy on the sevoflurane-induced cognitive dysfunction in aged rats, and to identify the role of autophagy in sevoflurane-induced neuron apoptosis. We used 20-month-old rats under sevoflurane anesthesia to study memory performance, neuron apoptosis, and autophagy. The results demonstrated that sevoflurane anesthesia significantly impaired memory performance and induced hippocampal neuron apoptosis. Interestingly, treatment of rapamycin, an autophagy inducer, improved the cognitive deficit observed in the aged rats under sevoflurane anesthesia by improving autophagic flux. Rapamycin treatment led to the rapid accumulation of autophagic bodies and autophagy lysosomes, decreased p62 protein levels, and increased the ratio of microtubule-associated protein light chain 3 II (LC3-II) to LC3-I in hippocampal neurons through the mTOR signaling pathway. However, administration of an autophagy inhibitor (chloroquine) attenuated the autophagic flux and increased the severity of sevoflurane anesthesia-induced neuronal apoptosis and memory impairment. These findings suggest that impaired autophagy in the hippocampal neurons of aged rats after sevoflurane anesthesia may contribute to cognitive impairment. Therefore, our findings represent a potential novel target for pro-autophagy treatments in patients with sevoflurane anesthesia-induced neurodegeneration.