Abstract：
Isoflurane is one of the most commonly used anaesthetic agents in surgery procedures. During the past decades, isoflurane has been found to cause impairment in neurological capabilities in new-borns and elderly patients. Luteolin is a flavonoid that has been documented to possess a neuroprotective effect. Here we investigated the putative neuroprotective effects of luteolin on isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells and explored the potential mechanisms. We demonstrated that luteolin improved mitochondrial dysfunction and reduced oxidative stress and apoptosis in isoflurane-treated HT22 cells, and thus inhibiting the isoflurane-induced neuronal injury. Further investigations showed that isoflurane exposure caused miR-214 downregulation, which could be mitigated by treatment with luteolin. Knockdown of miR-214 attenuated the neuroprotection of luteolin on isoflurane-induced neuronal injury. More importantly, luteolin inhibited isoflurane-caused regulation of the PTEN/Akt pathway, while miR-214 knockdown altered the regulatory effect of luteolin on the PTEN/Akt pathway. Furthermore, the effects of miR-214 knockdown on the neuroprotection of luteolin could also be prevented by knockdown of PTEN, implying that the neuroprotective effect of luteolin was mediated by miR-214/PTEN/Akt signaling pathway. These findings provided evidence for the potential application of luteolin in preventing isoflurane-induced neurotoxicity.
摘要：
异氟烷是外科手术中最常用的麻醉剂之一。在过去的几十年里，已发现异氟烷可导致新生儿和老年患者神经功能受损.木犀草素是一种类黄酮，已被证明具有神经保护作用。在这里，我们研究了木犀草素对异氟烷诱导的小鼠海马神经元HT22细胞神经毒性的假定神经保护作用，并探讨了潜在的机制。我们证明了木犀草素改善了异氟烷处理的HT22细胞的线粒体功能障碍并减少了氧化应激和凋亡，从而抑制异氟烷诱导的神经元损伤。进一步的研究表明，异氟烷暴露导致miR-214下调，可以通过木犀草素治疗来缓解。miR-214的敲低减弱木犀草素对异氟烷诱导的神经元损伤的神经保护作用。更重要的是,木犀草素抑制异氟烷引起的PTEN/Akt通路调节，而miR-214敲低改变木犀草素对PTEN/Akt通路的调节作用。此外，miR-214敲低对木犀草素的神经保护作用也可以通过敲低PTEN来阻止,提示木犀草素的神经保护作用是由miR-214/PTEN/Akt信号通路介导的。这些发现为木犀草素在预防异氟烷诱导的神经毒性方面的潜在应用提供了证据。
