Jian Rui, He Xin
Department of Rehabilitation Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
Transl Neurosci. 2023 Apr 11;14(1):20220282. doi: 10.1515/tnsci-2022-0282. eCollection 2023 Jan 1.
Anesthetic exposure causes learning and memory impairment, the mechanisms of which remain unknown. It has been reported that tumor necrosis factor-α-inducer protein 8-like 2 (TIPE2) is a newly discovered immune negative regulator that is essential for maintaining immune homeostasis. This study aimed to examine the role of TIPE2 in isoflurane-induced postoperative cognitive decline (POCD).
An AAV empty vector and AAV shTIPE2 vector for the knockdown of TIPE2 were injected into the dorsal hippocampus of mice. Mice were continuously exposed to 1.5% isoflurane followed by abdominal exploration. Behavioral tests including the open field test and fear conditioning test were performed on the third and fourth day post-operation. Apoptosis was detected by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. The kits were used to detect the activity of antioxidant enzymes. Inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) signaling pathway activities were detected by western blotting.
TIPE2 expression increased after isoflurane anesthesia and surgery. TIPE2 deficiency aggravated cognitive impairment in mice and further caused apoptosis and oxidative stress in hippocampal neurons. TIPE2 deficiency induced microglial activation and increased secretion of proinflammatory cytokines. In addition, TIPE2 deficiency promoted STAT3 and NF-κB signaling activation induced by isoflurane anesthesia and after surgery.
TIPE2 may play a neuroprotective role in POCD by regulating STAT3 and NF-κB pathways.
麻醉暴露会导致学习和记忆障碍，但其机制尚不清楚。据报道，肿瘤坏死因子-α诱导蛋白8样2（TIPE2）是一种新发现的免疫负调节因子，对维持免疫稳态至关重要。本研究旨在探讨TIPE2在异氟烷诱导的术后认知功能障碍（POCD）中的作用。
将AAV空载体和用于敲低TIPE2的AAV shTIPE2载体注入小鼠背侧海马体。小鼠持续暴露于1.5%异氟烷，随后进行腹部探查。在术后第三天和第四天进行包括旷场试验和恐惧条件试验在内的行为测试。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色检测细胞凋亡。使用试剂盒检测抗氧化酶的活性。通过酶联免疫吸附测定法检测炎性细胞因子水平。通过蛋白质印迹法检测信号转导和转录激活因子3（STAT3）和核因子-κB（NF-κB）信号通路的活性。
异氟烷麻醉和手术后TIPE2表达增加。TIPE2缺乏加重了小鼠的认知障碍，并进一步导致海马神经元凋亡和氧化应激。TIPE2缺乏诱导小胶质细胞活化并增加促炎细胞因子的分泌。此外，TIPE2缺乏促进了异氟烷麻醉和手术后诱导的STAT3和NF-κB信号激活。
TIPE2可能通过调节STAT3和NF-κB通路在POCD中发挥神经保护作用。
