老年小鼠術(shù)后認(rèn)知功能減退與炎癥分解通路功能障礙相關(guān)
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老年小鼠術(shù)后認(rèn)知功能減退與炎癥分解通路功能障礙相關(guān)
翻譯:任文鑫 編輯:馮玉蓉 審校:曹瑩
背景:術(shù)后認(rèn)知功能障礙(POCD)是指一種可逆的圍手術(shù)期精神障礙。POCD增加了術(shù)后并發(fā)癥的可能性和術(shù)后死亡的風(fēng)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(jīng)炎癥和認(rèn)知功能下降中的重要作用已被人們所認(rèn)識。我們推測老年小鼠的POCD可能與CAP功能障礙有關(guān)。
方法:將小鼠隨機(jī)分為五組(每組n=5):AM(成年小鼠)假手術(shù)組、AM(成年小鼠)手術(shù)組、EM(老年小鼠)假手術(shù)組、EM(老年小鼠)手術(shù)組和EM-P(伴有PNU的老年小鼠)手術(shù)組。術(shù)后24h評定認(rèn)知水平。采用酶聯(lián)免疫吸附試驗(yàn)(ELISA)和定量聚合酶鏈反應(yīng)(qPCR)檢測外周血和脾臟單核細(xì)胞的促炎細(xì)胞因子(TNF-α、IL-6和IL-10)。免疫熒光法檢測海馬M2巨噬細(xì)胞水平。流式細(xì)胞儀檢測脾臟CD11b/c+α7 nAChR+ 細(xì)胞。
結(jié)果:術(shù)后24小時,老年小鼠POCD較成年小鼠顯著升高。老年手術(shù)組小鼠(EM)的促炎因子TNF-α和IL-6高于成年手術(shù)組小鼠(AM)和老年-P手術(shù)組小鼠(EM-P);EM手術(shù)組小鼠的抗炎因子IL-10和M2巨噬細(xì)胞低于AM手術(shù)組小鼠和EM-P手術(shù)組小鼠。EM手術(shù)組小鼠脾細(xì)胞CD11b/c+α7 nAChR+ 細(xì)胞數(shù)量減少。
結(jié)論:老年小鼠過度且持續(xù)的認(rèn)知功能減退和炎癥反應(yīng)與CAP功能障礙有關(guān),α7nAch受體激動劑可逆轉(zhuǎn)這一現(xiàn)象。
文獻(xiàn)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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