Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, China.
Aging (Albany NY). 2023 Dec 4;15(24):14666-14676. doi: 10.18632/aging.205177.
Post-operative cognitive dysfunction (POCD) is a common complication after surgery due to the usage of anesthetics, such as Sevoflurane, which severely impacts the life quality of patients. Currently, the pathogenesis of Sevoflurane-induced POCD has not been fully elucidated but is reportedly involved with oxidative stress (OS) injury and aggravated inflammation. Phoenixin-20 (PNX-20) is a PNX peptide consisting of 20 amino acids with promising inhibitory effects on OS and inflammation. Herein, we proposed to explore the potential protective function of PNX-20 on Sevoflurane inhalation-induced POCD in rats. Sprague-Dawley (SD) rats were treated with 100 ng/g PNX-20 for 7 days with or without pre-inhalation with 2.2% Sevoflurane. Markedly increased escape latency and decreased time in the target quadrant in the Morris water maze (MWM) test, and aggravated pathological changes and apoptosis in the hippocampus tissue were observed in Sevoflurane-treated rats, which were markedly attenuated by PNX-20. Furthermore, the aggravated inflammation and OS in the hippocampus observed in Sevoflurane-treated rats were notably abolished by PNX-20. Moreover, the brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), and phospho-cAMP response element binding protein/cAMP response element binding protein (p-CREB/CREB) levels were markedly decreased in Sevoflurane-treated rats, which were memorably increased by PNX-20. Our results indicated that PNX-20 ameliorated Sevoflurane inhalation-induced POCD in rats via the activation of PKA/CREB signaling, which might supply a new treatment approach for POCD.
术后认知功能障碍（POCD）是一种常见的手术并发症，由于麻醉剂的使用，如七氟醚，这严重影响了患者的生活质量。目前，七氟醚诱导的 POCD 的发病机制尚未完全阐明，但据报道与氧化应激（OS）损伤和炎症加重有关。凤凰素-20（PNX-20）是一种由 20 个氨基酸组成的 PNX 肽，对 OS 和炎症具有有希望的抑制作用。在此，我们提出探讨 PNX-20 对大鼠七氟醚吸入诱导的 POCD 的潜在保护作用。SD 大鼠用 100ng/g 的 PNX-20 处理 7 天，同时或不预先吸入 2.2%的七氟醚。Morris 水迷宫（MWM）测试中观察到逃避潜伏期明显延长，目标象限时间减少，海马组织病理变化和细胞凋亡加重，PNX-20 明显减轻。此外，PNX-20 明显消除了七氟醚处理大鼠海马中加重的炎症和 OS。此外，七氟醚处理大鼠的脑源性神经营养因子（BDNF）、蛋白激酶 A（PKA）和磷酸-cAMP 反应元件结合蛋白/cAMP 反应元件结合蛋白（p-CREB/CREB）水平明显降低，PNX-20 明显增加。我们的结果表明，PNX-20 通过激活 PKA/CREB 信号通路改善了大鼠的七氟醚吸入诱导的 POCD，这可能为 POCD 提供了一种新的治疗方法。
