Department of Anesthesiology, The Sixth People's Hospital East Campus, Shanghai University of Medicine and Health Sciences, Shanghai 200233, P.R. China.
Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.
Mol Med Rep. 2018 Jun;17(6):7730-7736. doi: 10.3892/mmr.2018.8850. Epub 2018 Apr 5.
Elderly patients are at high risk of developing postoperative cognitive dysfunction (POCD) after prolonged exposure to inhaled anesthetics. However, the pathogenesis of POCD remains unknown. Hypoxia‑inducible factor‑1α (HIF‑1α) is activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF‑1α in isoflurane‑induced neuroinflammation and the resulting cognitive impairment. Following a 4‑h exposure to 1.5% isoflurane in 20‑month‑old rats, increased expression of HIF‑1α protein, activation of nuclear factor (NF)‑κB signaling and increased expression of TNF‑1α were observed in the hippocampus of isoflurane‑exposed rats compared with the control group. Pharmacological inhibition of HIF‑1α activation by 5‑[1‑(phenylmethyl)‑1H‑indazol‑3‑yl]‑2‑furanmethanol (YC‑1) markedly suppressed the enhanced expression of HIF‑1α, disrupted NF‑κB signaling pathway activity and inhibited the isoflurane‑induced increase of TNF‑1α expression. YC‑1 pretreatment also significantly attenuated isoflurane‑induced cognitive deficits according to the results of the Morris water maze task. These results suggest that hippocampal HIF‑1α appears to be involved in an upstream mechanism of isoflurane‑induced cognitive impairment. Further research is warranted to fully clarify the pathogenesis and investigate HIF‑1α as a potential therapeutic target for POCD.
老年患者在长时间接触吸入麻醉剂后，发生术后认知功能障碍（POCD）的风险较高。然而，POCD 的发病机制尚不清楚。缺氧诱导因子-1α（HIF-1α）可被吸入麻醉剂激活。本研究旨在确定 HIF-1α 在异氟醚诱导的神经炎症及由此导致的认知障碍中的作用。在 20 月龄大鼠中暴露于 1.5%异氟醚 4 小时后，与对照组相比，异氟醚暴露组大鼠海马中 HIF-1α 蛋白表达增加，核因子（NF）-κB 信号通路激活，TNF-α1 表达增加。5-[1-（苯基甲基）-1H-吲哚-3-基]-2-呋喃甲醇（YC-1）通过抑制 HIF-1α 的激活，可显著抑制 HIF-1α 的增强表达，破坏 NF-κB 信号通路活性，并抑制异氟醚诱导的 TNF-α1 表达增加。根据 Morris 水迷宫任务的结果，YC-1 预处理也显著减轻了异氟醚诱导的认知功能障碍。这些结果表明，海马 HIF-1α 似乎参与了异氟醚诱导的认知障碍的上游机制。需要进一步研究以充分阐明发病机制，并研究 HIF-1α 作为 POCD 的潜在治疗靶点。
