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老年小鼠術后認知功能減退與炎癥分解通路功能障礙相關

翻譯：任文鑫  編輯：馮玉蓉  審校：曹瑩

背景：術后認知功能障礙(POCD)是指一種可逆的圍手術期精神障礙。POCD增加了術后并發(fā)癥的可能性和術后死亡的風險，尤其是老年患者(65歲或以上)。膽堿能抗炎通路(CAP)在分解無菌創(chuàng)傷引起的神經炎癥和認知功能下降中的重要作用已被人們所認識。我們推測老年小鼠的POCD可能與CAP功能障礙有關。

方法：將小鼠隨機分為五組(每組n=5)：AM(成年小鼠)假手術組、AM(成年小鼠)手術組、EM(老年小鼠)假手術組、EM(老年小鼠)手術組和EM-P(伴有PNU的老年小鼠)手術組。術后24h評定認知水平。采用酶聯(lián)免疫吸附試驗(ELISA)和定量聚合酶鏈反應(qPCR)檢測外周血和脾臟單核細胞的促炎細胞因子(TNF-α、IL-6和IL-10)。免疫熒光法檢測海馬M2巨噬細胞水平。流式細胞儀檢測脾臟CD11b/c+α7 nAChR+ 細胞。

結果：術后24小時，老年小鼠POCD較成年小鼠顯著升高。老年手術組小鼠(EM)的促炎因子TNF-α和IL-6高于成年手術組小鼠(AM)和老年-P手術組小鼠(EM-P)；EM手術組小鼠的抗炎因子IL-10和M2巨噬細胞低于AM手術組小鼠和EM-P手術組小鼠。EM手術組小鼠脾細胞CD11b/c+α7 nAChR+ 細胞數(shù)量減少。

結論：老年小鼠過度且持續(xù)的認知功能減退和炎癥反應與CAP功能障礙有關，α7nAch受體激動劑可逆轉這一現(xiàn)象。

文獻來源：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.

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