Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Otolaryngology, Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Behav Brain Res. 2020 Feb 3;379:112344. doi: 10.1016/j.bbr.2019.112344. Epub 2019 Nov 7.
The pathogenesis of postoperative cognitive impairment of obstructive sleep apnea-hypopnea syndrome (OSAHS) individuals remains unclear. AMP activated protein kinase (AMPK) is a ubiquitous sensor/effector of cell stresses. Thus we detected the role and underlying mechanisms of AMPK in postoperative cognitive impairment of OSAHS individuals in intermittent hypoxia rats. Cognitive function was evaluated by novel object recognition test and Barnes maze during the first 4 days after laparotomy. We found that laparotomy induced postoperative cognitive impairment and AMPK activation in intermittent hypoxia rats, but not in adult rats. Inhibiting AMPK activation via Compound C during laparotomy improved postoperative cognitive impairment and alleviated surgery-induced upregulation of p-PAK2, AMPK-PAK2 complex, and neuroinflammation (marked by microglial activation and IL-1β level) in intermittent hypoxia rats. These data suggested that AMPK played an important role in postoperative cognitive impairment of OSAHS individuals via directly activating PAK2.
阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者术后认知功能障碍的发病机制尚不清楚。AMP 激活蛋白激酶（AMPK）是细胞应激的普遍传感器/效应器。因此，我们检测了 AMPK 在间歇性低氧大鼠 OSAHS 患者术后认知障碍中的作用及其潜在机制。在剖腹术后的前 4 天，通过新物体识别测试和 Barnes 迷宫评估认知功能。我们发现，剖腹术引起间歇性低氧大鼠术后认知功能障碍和 AMPK 激活，但在成年大鼠中则没有。在剖腹术中通过化合物 C 抑制 AMPK 激活可改善术后认知功能障碍，并减轻手术引起的 p-PAK2、AMPK-PAK2 复合物和神经炎症（以小胶质细胞激活和 IL-1β 水平为标志）的上调。这些数据表明，AMPK 通过直接激活 PAK2 在 OSAHS 患者术后认知障碍中发挥重要作用。
