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异荭草苷通过激活 PGC-1α/FNDC5 信号通路介导自噬来恢复七氟醚诱导的认知功能障碍。

Isovitexin restores sevoflurane‑induced cognitive dysfunction by mediating autophagy through activation of the PGC‑1α/FNDC5 signaling pathway.

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;

Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Acta Neurobiol Exp (Wars). 2022;82(3):373-379. doi: 10.55782/ane-2022-035.

Abstract

Postoperative cognitive dysfunction is a severe neurological complication. How to improve the cognitive impairment caused by sevoflurane, a most common inhaled anesthetic, remains a question worthy of studying. Isovitexin (IVX) is a trihydroxyl flavonoid that is a naturally bioactive ingredient found in various medicinal plants and has antioxidant, anti‑inflammatory and neuroprotective properties. The role of IVX in anesthetic‑induced nerve injury is rarely reported and the mechanisms are unclear. In this study, we found that IVX improved the cognitive dysfunction induced by sevoflurane in rats. It inhibited sevoflurane‑induced cell apoptosis. In addition, IVX increased sevoflurane‑induced autophagy in rat brain. Mechanically, IVX activated the PGC‑1α/FNDC5 pathway in rat brain, and depletion of FNDC5 could inhibit the neuroprotective function of IVX. In conclusion, our results suggested that IVX restored sevoflurane‑induced cognitive dysfunction by mediating autophagy through the activation of the PGC‑1α/FNDC5 pathway.

摘要

术后认知功能障碍是一种严重的神经系统并发症。如何改善七氟醚(最常用的吸入性麻醉剂)引起的认知障碍仍是一个值得研究的问题。异牡荆黄素(IVX)是一种三羟基黄酮类化合物,是多种药用植物中发现的天然生物活性成分,具有抗氧化、抗炎和神经保护作用。IVX 在麻醉诱导的神经损伤中的作用很少有报道,其机制尚不清楚。在这项研究中,我们发现 IVX 可改善七氟醚诱导的大鼠认知功能障碍。它抑制七氟醚诱导的细胞凋亡。此外,IVX 增加了七氟醚诱导的大鼠脑自噬。从机制上讲,IVX 在大鼠脑中激活了 PGC-1α/FNDC5 通路,而 FNDC5 的耗竭可以抑制 IVX 的神经保护功能。总之,我们的结果表明,IVX 通过激活 PGC-1α/FNDC5 通路介导自噬来恢复七氟醚诱导的认知功能障碍。

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