AMPK-SIRT1通路功能障碍参与七氟烷诱导的神经元凋亡和认知损伤

Abstract

The anesthetic sevoflurane (Sev) is widely used because of its low blood‑gas partition coefficient and lack of pungency. However, the application of Sevmay lead to cognitive impairment later in life. Previous results have indicated that exposure to Sev‑induced neuronal apoptosis and cognitive dysfunction in a rat model, but much work remains to elucidate the mechanism. In the present study, inhibition in the AMP‑activated protein kinase/Sirtuin 1 (AMPK/SIRT1) signaling pathway and a decrease in AMPK/SIRT1 activity was found to occur concomitantly in neuronal apoptosis induced by Sev. AICAR, an activator of AMPK, was able to suppress Sev‑induced neuronal apoptosis and SIRT1 activity reduction in vitro. Further animal studies also showed that AICAR treatment blocked the deleterious cognition and AMPK/SIRT1 activity reduction in the cognition impairment rats induced by Sev. Taken together, it was concluded that the AMPK/SIRT1 signaling pathway mediates neuronal apoptosis and cognition impairment induced by Sev. The study provides evidence that AMPK activation ameliorates Sev‑induced cognitive deficits.