Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system complication, especially in the elderly. It has been consistently reported that the pathological process of this clinical syndrome is related to neuroinflammation and microglial proliferation. Glycogen synthase kinase 3β (GSK-3β) is a widely expressed kinase with distinct functions in different types of cells. The role of GSK-3β in regulating innate immune activation has been well documented, but as far as we know, its role in POCD has not been fully elucidated. Lithium chloride (LiCl) is a widely used inhibitor of GSK-3β, and it is also the main drug for the treatment of bipolar disorder. Prophylactic administration of lithium chloride (2 mM/kg) can inhibit the expression of proinflammatory mediators in the hippocampus, reduce the hippocampal expression of NF-κB, and increase both the downregulation of M1 microglial-related genes (inducible nitric oxide synthase and CD86) and upregulation of M2 microglial-related genes (IL-10 and CD206), to alleviate the cognitive impairment caused by orthopedic surgery. In vitro, LiCl reversed LPS-induced production of proinflammatory mediators and M1 polarization of microglia. To sum up these results, GSK-3β is a key contributor to POCD and a potential target of neuroprotective strategies.

中文翻译：

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糖原合酶激酶 3β 通过诱导小胶质细胞 M1 极化和迁移促进术后认知功能障碍

术后认知功能障碍（POCD）是一种常见的术后中枢神经系统并发症，尤其是老年人。一直有报道称，该临床综合征的病理过程与神经炎症和小胶质细胞增殖有关。糖原合酶激酶 3 β (GSK-3 β ) 是一种广泛表达的激酶，在不同类型的细胞中具有不同的功能。GSK-3 β在调节先天免疫激活中的作用已被充分证明，但据我们所知，其在 POCD 中的作用尚未完全阐明。氯化锂 (LiCl) 是一种广泛使用的 GSK-3 β抑制剂，也是治疗双相情感障碍的主要药物。（2毫摩尔/千克）的氯化锂预防性给药可以抑制促炎介质的表达在海马，减少NF-海马表达κ B，并增加小胶质细胞M1相关基因两者的下调（诱导型一氧化氮合酶和CD86 ) 和 M2 小胶质细胞相关基因 (IL-10 和 CD206) 的上调，以减轻骨科手术引起的认知障碍。在体外，LiCl 逆转了 LPS 诱导的促炎介质的产生和小胶质细胞的 M1 极化。总结这些结果，GSK-3 β是 POCD 的关键因素，也是神经保护策略的潜在目标。