Li Xiuhua, Gao Yubo, Han Xu, Tang Shaling, Li Na, Liu Xing, Ni Xinli
Department of Anaesthesia and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Department of Anaesthesia and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Exp Gerontol. 2023 Jun 1;176:112168. doi: 10.1016/j.exger.2023.112168. Epub 2023 Apr 13.
Postoperative cognitive dysfunction (POCD) is one of the most serious postoperative complications in the elderly population. Perioperative central neuroinflammation is considered to be an important pathological mechanism of POCD, with the activation of astrocytes playing a key role in central neuroinflammation. Maresin1 (MaR1) is a specific pro-resolving mediator synthesized by macrophages in the resolution stage of inflammation, and provides unique anti-inflammatory and pro-resolution effects by limiting excessive neuroinflammation and promoting postoperative recovery. However, the question remains whether MaR1 can have a positive effect on POCD. The objective of this study was to investigate the protective effect of MaR1 on POCD cognitive function in aged rats after splenectomy. Morris water maze test and IntelliCage test showed that splenectomy could cause transient cognitive dysfunction in aged rats; however, the cognitive impairment of rats was significantly mitigated when MaR1 pretreatment was administered. MaR1 significantly alleviated the fluorescence intensity and protein expression of glial fibrillary acidic protein and central nervous system specific protein in the cornu ammonis 1 region of the hippocampus. Simultaneously, the morphology of astrocytes was also severely altered. Further experiments showed that MaR1 inhibited the mRNA and protein expression of several key proinflammatory cytokines-interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampus of aged rats following splenectomy. The molecular mechanism underlying this process was explored by evaluating expression of components of the nuclear factor κB (NF-κB) signaling pathway. MaR1 substantially inhibited the mRNA and protein expression of NF-κB p65 and κB inhibitor kinase β. Collectively, these results suggest that MaR1 ameliorated splenectomy-induced transient cognitive impairment in elderly rats, and this neuroprotective mechanism may occur through regulating the NF-κB pathway to inhibit astrocyte activation.
术后认知功能障碍（POCD）是老年人群中最严重的术后并发症之一。围手术期中枢神经炎症被认为是POCD的重要病理机制，星形胶质细胞的激活在中枢神经炎症中起关键作用。maresin1（MaR1）是巨噬细胞在炎症消退阶段合成的一种特异性促消退介质，通过限制过度的神经炎症和促进术后恢复发挥独特的抗炎和促消退作用。然而，MaR1是否能对POCD产生积极影响仍存在疑问。本研究的目的是探讨MaR1对老年大鼠脾切除术后POCD认知功能的保护作用。莫里斯水迷宫试验和智能笼试验表明，脾切除术可导致老年大鼠短暂性认知功能障碍；然而，给予MaR1预处理后，大鼠的认知障碍明显减轻。MaR1显著减轻了海马齿状回1区胶质纤维酸性蛋白和中枢神经系统特异性蛋白的荧光强度和蛋白表达。同时，星形胶质细胞的形态也发生了严重改变。进一步实验表明，MaR1抑制了老年大鼠脾切除术后海马中几种关键促炎细胞因子白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α的mRNA和蛋白表达。通过评估核因子κB（NF-κB）信号通路成分的表达来探索这一过程的分子机制。MaR1显著抑制了NF-κB p65和κB抑制激酶β的mRNA和蛋白表达。总的来说，这些结果表明MaR1改善了脾切除术诱导的老年大鼠短暂性认知障碍，这种神经保护机制可能是通过调节NF-κB通路来抑制星形胶质细胞激活而发生的。
