Fang Qian-Juan, Chi Bing-Huan, Lin Qi-Cheng, Huang Chen-Miao, Jin Shao-Wu, Cai Jia-Jing, Nan Ke, Han Yuan, Tao Yuan-Xiang, Cao Hong, Li Jun
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Zhejiang Province Key Lab of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Am J Transl Res. 2020 Dec 15;12(12):8111-8122. eCollection 2020.
Elderly patients often suffer from cognitive dysfunction following surgery. However, the mechanisms underlying this phenomenon still remain unclear. This study investigated the critical part of Sirtuin-1 (SIRT1)-mediated autophagy and apoptosis in surgery-induced cognitive impairment.
The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein.
This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3.
These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis.
老年患者术后常出现认知功能障碍。然而，这一现象背后的机制仍不清楚。本研究调查了沉默调节蛋白1（SIRT1）介导的自噬和凋亡在手术诱导的认知障碍中的关键作用。
对16月龄雄性C57BL/6小鼠进行麻醉和手术。部分小鼠在接受脾切除术之前腹腔注射白藜芦醇（一种SIRT1激活剂）。为检测不同组别的学习和记忆行为，本研究进行了莫里斯水迷宫实验。术后1天、3天和7天采集海马组织。通过蛋白质免疫印迹法和免疫荧光分析确定自噬和凋亡相关蛋白的表达。
本文证明手术而非麻醉对老年小鼠的记忆行为有显著影响，并下调了SIRT1的表达。有趣的是，恢复海马SIRT1表达可改善老年小鼠脾切除术后的认知障碍。此外，手术创伤降低了Beclin-1蛋白水平和LC3-II/LC3-I比值，而海马神经元中p62、Bax和裂解的caspase-3的表达增加。然而，恢复海马SIRT1表达可显著减弱手术诱导的Beclin-1下调，增加LC3-II/LC3-I比值，并降低p62、Bax和裂解的caspase-3的表达。
这些发现表明，手术诱导的海马SIRT1下调通过抑制自噬过程和激活凋亡参与术后认知障碍。
