Department of Anesthesiology, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PeerJ. 2024 Nov 15;12:e18507. doi: 10.7717/peerj.18507. eCollection 2024.
Cirsilineol is a trimethoxy and dihydroxy flavonoid isolated from plant species such as and has a variety of pharmacological properties. This study analyzed whether cirsilineol could prevent postoperative cognitive dysfunction (POCD).
A POCD mouse model induced by anesthesia/surgery induction and a cell model established with hydrogen peroxide (HO)-induced microglia BV-2 were employed to explore the efficacy of cirsilineol on POCD. The cognition function of the mice were assessed by carrying out behavioral tests (Morris water maze test and Y-maze test). We assessed the activation and polarization status of microglia using immunofluorescence analysis and detected the expression levels of CD86 and CD206 using the quantitative PCR (qPCR). Subsequently, cell viability was determined by CCK-8 assay and apoptosis was assessed using Calcein-AM/PI staining. Meanwhile, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in plasma and cell culture medium were detected using chemiluminescence. Finally, the phosphorylation levels of JAK/STAT signaling pathway-related proteins were analyzed by Western blot.
Cirsilineol reduced the escape latency and times of crossing island and increased spontaneous alternation (SA) rate, restoring the cognitive dysfunctions of POCD-modeled mice. Meanwhile, POCD elevated CD86 expression and malondialdehyde content and lowered the level of SOD; however, cirsilineol promoted CD206 expression and generation of SOD and inhibited malondialdehyde production. In HO-induced microglia BV-2, cirsilineol treatment increased SOD content and suppressed the generation of reactive oxygen species (ROS) and malondialdehyde, modulating microglia M1/M2 polarization and JAK/STAT pathway.
Cirsilineol prevented against POCD by attenuating oxidative stress and modulating microglia M1/M2 polarization, providing novel insights for the management of POCD.
齿叶乳香素是一种从植物物种中分离出来的三甲氧基和二羟基黄酮，具有多种药理学特性。本研究分析了齿叶乳香素是否可以预防术后认知功能障碍（POCD）。
采用麻醉/手术诱导的 POCD 小鼠模型和过氧化氢（HO）诱导的小胶质细胞 BV-2 细胞模型，探讨齿叶乳香素对 POCD 的疗效。通过行为测试（Morris 水迷宫测试和 Y 迷宫测试）评估小鼠的认知功能。使用免疫荧光分析评估小胶质细胞的激活和极化状态，并使用定量 PCR（qPCR）检测 CD86 和 CD206 的表达水平。随后，通过 CCK-8 测定法测定细胞活力，通过 Calcein-AM/PI 染色测定细胞凋亡。同时，使用化学发光法检测血浆和细胞培养液中超氧化物歧化酶（SOD）和丙二醛（MDA）水平。最后，通过 Western blot 分析 JAK/STAT 信号通路相关蛋白的磷酸化水平。
齿叶乳香素降低了逃避潜伏期和穿越岛屿的次数，增加了自发交替（SA）率，恢复了 POCD 模型小鼠的认知功能障碍。同时，POCD 增加了 CD86 的表达和丙二醛的含量，降低了 SOD 的水平；然而，齿叶乳香素促进了 CD206 的表达和 SOD 的生成，并抑制了丙二醛的产生。在 HO 诱导的小胶质细胞 BV-2 中，齿叶乳香素处理增加了 SOD 的含量，抑制了活性氧（ROS）和丙二醛的生成，调节了小胶质细胞 M1/M2 极化和 JAK/STAT 通路。
齿叶乳香素通过减轻氧化应激和调节小胶质细胞 M1/M2 极化来预防 POCD，为 POCD 的管理提供了新的思路。
