老年小鼠术后认知功能减退与炎症分解通路功能障碍相关

背景：术后认知功能障碍(POCD)是指一种可逆的围手术期精神障碍。POCD增加了术后并发症的可能性和术后死亡的风险，尤其是老年患者(65岁或以上)。胆碱能抗炎通路(CAP)在分解无菌创伤引起的神经炎症和认知功能下降中的重要作用已被人们所认识。我们推测老年小鼠的POCD可能与CAP功能障碍有关。

方法：将小鼠随机分为五组(每组n=5)：AM(成年小鼠)假手术组、AM(成年小鼠)手术组、EM(老年小鼠)假手术组、EM(老年小鼠)手术组和EM-P(伴有PNU的老年小鼠)手术组。术后24h评定认知水平。采用酶联免疫吸附试验(ELISA)和定量聚合酶链反应(qPCR)检测外周血和脾脏单核细胞的促炎细胞因子(TNF-α、IL-6和IL-10)。免疫荧光法检测海马M2巨噬细胞水平。流式细胞仪检测脾脏CD11b/c+α7 nAChR+ 细胞。

结果：术后24小时，老年小鼠POCD较成年小鼠显著升高。老年手术组小鼠(EM)的促炎因子TNF-α和IL-6高于成年手术组小鼠(AM)和老年-P手术组小鼠(EM-P)；EM手术组小鼠的抗炎因子IL-10和M2巨噬细胞低于AM手术组小鼠和EM-P手术组小鼠。EM手术组小鼠脾细胞CD11b/c+α7 nAChR+ 细胞数量减少。

结论：老年小鼠过度且持续的认知功能减退和炎症反应与CAP功能障碍有关，α7nAch受体激动剂可逆转这一现象。

文献来源：Gong M, Wang G, Li G, et al. Dysfunction of Inflflammation-Resolving Pathways Is Associated with Postoperative Cognitive Decline in Elderly Mice.Behav Brain Res 2020 May 27;386. DOI：10.1016/j.bbr.2020.112538.

Dysfunction of Inflammation-Resolving Pathways Is Associated with Postoperative Cognitive Decline in Elderly Mice

Abstract

Background: Postoperative cognitive dysfunction (POCD) refers to a reversible, perioperative mental disorder. POCD increases the likelihood of postoperative complications and the risk for postoperative mortality, typically among elderly patients (age 65 or older). The importance of the cholinergic anti-inflammatory pathway (CAP) in resolving neuro-inflammatory and cognitive decline caused by sterile trauma has been recognized. We speculate that the POCD in elderly mice is associated with dysfunction of CAP.

Methods: Mice were assigned to several groups (n = 5 in each group): AM (adult mice) Sham, AM (adult mice) Surgery, EM (elderly mice) Sham, EM (elderly mice) Surgery, and EM-P (elderly mice with PNU) Surgery. At 24h after surgery, assessed the cognitive levels. Pro-inflammatory cytokines in peripheral blood and splenic monocytes (TNF-α, IL-6 and IL-10) were assessed by ELISA and qPCR. Levels of M2 macrophages in hippocampus were visualized by immunofluorescence. Detecting CD11b/c+α7 nAChR+ cells in the spleens with flow cytometry.

Results: At postoperative 24 hours, elderly mice exhibited significantly increased POCD compared with adult mice. The proinflammatory factor TNF-α and IL-6 were higher among elderly surgery mice (EM) compared with adult surgery (AM) and elderly-P surgery mice (EM-P); the anti-inflammatory factor IL-10 and M2 macrophages were lower among EM surgery mice compared with AM surgery and EM-P surgery mice. The CD11b/c+α7 nAChR+ population of splenocytes was reduced in the EM surgery mice.

Conclusions: The exaggerated and persistent cognitive decline and inflammatory response among elderly mice were associated with dysfunction of CAP, and these phenomena were reversed by α7nAch receptor agonists.