吗啡术后镇痛促进手术引起的小胶质细胞激活和神经炎症加重老年小鼠围手术期神经认知功能障碍。

IF 2 Q3 NEUROSCIENCES
Xiuzhi Shao , Liping Xie , Jingwen Zhai , Mingyue Ge
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引用次数: 0

摘要

围手术期神经认知功能障碍(PND)是世界范围内需要手术的患者面临的重大挑战。吗啡在镇痛的同时可引起中枢神经系统强烈的炎症反应,从而加重PND的不良反应。小胶质细胞极化密切参与神经炎症和TLR4/MyD88/NF-κB信号通路的调控。然而,吗啡镇痛加重PND损害的机制尚不清楚。方法:对18月龄雄性C57BL/6 J小鼠进行胫骨骨折手术,模拟人类骨科手术及术后吗啡或罗哌卡因皮下注射镇痛。在手术和术后镇痛后,评估海马炎症因子水平、TLR4/MyD88/NF-κB信号通路必需蛋白小胶质细胞的激活和表型、突触可塑性和海马依赖记忆功能。结果:吗啡术后镇痛增加了促炎细胞因子IL-1 β、IL-6、TNF-α的表达,降低了抗炎细胞IL-10的水平,加重了海马小胶质细胞的激活和突触可塑性的破坏,导致老年小鼠海马神经元丢失,突触数量明显减少,认知功能受损。此外,TLR4/MyD88/NF- κ B信号通路可能介导了神经炎症反应的加重和小胶质细胞的活化。结论:吗啡术后镇痛可能通过调节TLR4/MyD88/NF- κ B信号通路,抑制海马神经元突触可塑性,加重海马小胶质细胞活化和神经炎症。它加重了老年小鼠胫骨骨折后的急性认知能力下降和认知功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Postoperative analgesia with morphine promoting microglial activation and neuroinflammation induced by surgery aggravates perioperative neurocognitive dysfunction in aged mice

Introduction

Perioperative neurocognitive dysfunction (PND) is a significant challenge for patients who need surgery worldwide. Morphine can trigger an intense inflammatory reaction in the central nervous system (CNS) at the same time as analgesia, thus adverse effects aggravating PND. Microglia polarization is closely involved in the regulation of neuroinflammation and the TLR4/MyD88/NF-κB signaling pathway. However, the mechanisms of morphine analgesia aggravating PND impairment remain unclear.

Methods

Tibial fracture surgery was performed in 18 months old male C57BL/6 J mice to mimic human orthopedic surgery and postoperative analgesia with morphine hypodermic or ropivacaine. Levels of inflammatory factors in the hippocampus, activation, and phenotype of microglia, an essential protein of TLR4/MyD88/NF-κB signal pathway, synaptic plasticity, and hippocampal-dependent memory function were evaluated after surgery and postoperative analgesia.

Results

Morphine postoperative analgesia increased the expression of pro-inflammatory cytokines IL-1 β, IL-6, and TNF-α, decreased the level of anti-inflammatory IL-10, aggravated the activation of microglia and the destruction of synaptic plasticity in the hippocampus, resulting in hippocampal neuron loss, a significant decrease in the number of synapses and cognitive impairment in aged mice. In addition, the aggravation of neuroinflammatory response and the activation of microglia may be mediated by TLR4/MyD88/NF- κ B signal pathway.

Conclusion

Our results demonstrate that morphine postoperative analgesia may aggravate microglia activation and neuroinflammation in the hippocampus by regulating the TLR4/MyD88/NF- κ B signal pathway and inhibiting the synaptic plasticity hippocampal neurons. It aggravated the acute cognitive decline and cognitive impairment after tibial fracture in elderly mice.
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来源期刊
IBRO Neuroscience Reports
IBRO Neuroscience Reports Neuroscience-Neuroscience (all)
CiteScore
2.80
自引率
0.00%
发文量
99
审稿时长
14 weeks
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