Yuan Na, Wang Xiuzhen, Zhang Yu, Kong Lingsi, Yuan Liyong, Ge Yeying
Department of Anaesthesia, Ningbo NO.6 Hospital, Zhejiang 315040, China.
Iran J Public Health. 2022 Jan;51(1):124-132. doi: 10.18502/ijph.v51i1.8303.
The Postoperative cognitive dysfunction (POCD) model was constructed by resection of the left hepatic lobe in aged mice to determine the behavioral effects of the POCD model in aged mice and the relationship between NF-κB and POCD in apoptosis and autophagy. Provide a theoretical basis for POCD prevention and treatment.
This study was carried out in Ningbo No. 6 Hospital, Zhejiang, China, from Jun 2019 to Dec 2020. The POCD model was constructed after resection of the left extrahepatic lobe in aged mice and randomly divided into 6 groups: sham operation group, operation group (normal saline control group, solvent group, YC-1 group, PDTC group and 3-MA group). Related indicators of behavioral changes, neuronal inflammatory responses, apoptosis, and autophagy were examined.
The escape latency of the aged mice in the surgical group was significantly prolonged at three time points compared with the control group, and the number of insertions decreased significantly. Microglia are activated and the inflammatory response is increased, whereas PDTC has an inhibitory effect. It was demonstrated that apoptosis and necrosis of neurons can be induced by the NF-κb pathway, and autophagy can be promoted, whereas autophagy occurs before apoptosis.
Activation of NF-κb pathway in neurons after POCD causes neuronal apoptosis and autophagy, and cognitive impairment occurs. PDTC, a NF-κb pathway inhibitor, can effectively reduce neuronal apoptosis induced by secondary brain injury after POCD. Necrosis, to protect the brain tissue.
通过切除老年小鼠的左肝叶构建术后认知功能障碍(POCD)模型,以确定POCD模型对老年小鼠行为的影响以及核因子κB(NF-κB)与POCD在细胞凋亡和自噬中的关系。为POCD的防治提供理论依据。
本研究于2019年6月至2020年12月在中国浙江宁波第六医院进行。在老年小鼠切除肝外左叶后构建POCD模型,并随机分为6组:假手术组、手术组(生理盐水对照组、溶剂组、YC-1组、PDTC组和3-MA组)。检测行为变化、神经元炎症反应、细胞凋亡和自噬的相关指标。
与对照组相比,手术组老年小鼠在三个时间点的逃避潜伏期显著延长,穿格次数显著减少。小胶质细胞激活,炎症反应增强,而PDTC具有抑制作用。结果表明,NF-κb途径可诱导神经元凋亡和坏死,并促进自噬,且自噬发生在凋亡之前。
POCD后神经元中NF-κb途径的激活导致神经元凋亡和自噬,并出现认知障碍。NF-κb途径抑制剂PDTC可有效减少POCD后脑继发性损伤诱导的神经元凋亡、坏死,保护脑组织。