Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Institute of Cardiovascular Diseases, Tianjin Chest Hospital, Tianjin 300457, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11694. Epub 2020 Nov 17.
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.
麻醉剂七氟醚（Sev）因其血液-气体分配系数低且无刺激性而被广泛应用。然而，七氟醚的应用可能会导致日后认知障碍。先前的结果表明，七氟醚在大鼠模型中会引起神经元凋亡和认知功能障碍，但仍有许多工作需要阐明其机制。在本研究中，发现 Sev 诱导的神经元凋亡伴随着 AMP 激活的蛋白激酶/沉默调节蛋白 1（AMPK/SIRT1）信号通路的抑制和 AMPK/SIRT1 活性的降低。AICAR，一种 AMPK 的激活剂，能够抑制 Sev 诱导的神经元凋亡和 SIRT1 活性降低体外。进一步的动物研究还表明，AICAR 治疗可阻断 Sev 诱导的认知障碍大鼠的认知障碍和 AMPK/SIRT1 活性降低。综上所述，结论认为 AMPK/SIRT1 信号通路介导 Sev 诱导的神经元凋亡和认知障碍。该研究为 AMPK 激活改善 Sev 诱导的认知缺陷提供了证据。
