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银杏内酯 B 通过抑制小胶质细胞介导的神经炎症改善了小鼠海马区的术后认知功能障碍。

Ginkgolide B improved postoperative cognitive dysfunction by inhibiting microgliosis-mediated neuroinflammation in the hippocampus of mice.

机构信息

Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, Beijing, 100020, China.

出版信息

BMC Anesthesiol. 2022 Jul 18;22(1):229. doi: 10.1186/s12871-022-01750-1.

DOI:10.1186/s12871-022-01750-1
PMID:35850641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9290278/
Abstract

BACKGROUND

Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats.

METHODS

Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus.

RESULTS

Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1β and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats.

CONCLUSION

Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats.

摘要

背景

术后认知功能障碍(POCD)是中枢神经系统手术后和麻醉后的常见并发症。POCD 的具体发病机制和有效治疗方法需要进一步研究。银杏内酯 B(GB)是一种血小板激活因子受体特异性拮抗剂,具有很强的抗炎作用。在这里,我们测试了 GB 预处理对老年大鼠 POCD 的影响及其机制。

方法

神经行为学测试用于研究 GB 预处理对 POCD 的影响。通过 ELISA 检测海马中促炎细胞因子的表达。通过 Western blot 分析和免疫组织化学检测海马中小胶质细胞标志物离子钙结合衔接分子 1(Iba-1)的表达。尼氏染色实验用于检测海马中的神经元数量。

结果

手术可能导致血浆和海马中血小板激活因子(PAF)的过度表达,并可能导致海马依赖性记忆障碍。GB 预处理抑制了小胶质细胞的激活,降低了 IL-1β 和 TNF-α 的水平,减少了手术后神经元的丢失,并预防了老年大鼠的 POCD。

结论

我们的研究结果表明 PAF 参与了 POCD 的发生。PAF 拮抗剂 GB 改善 POCD 与抑制小胶质细胞介导的神经炎症和老年大鼠神经元凋亡有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/756ca9f72e91/12871_2022_1750_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/08d708b8a636/12871_2022_1750_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/ab8e5e1965c8/12871_2022_1750_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/d75438f8d4c0/12871_2022_1750_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/56fbaff13fa1/12871_2022_1750_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/756ca9f72e91/12871_2022_1750_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/08d708b8a636/12871_2022_1750_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/ab8e5e1965c8/12871_2022_1750_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/d75438f8d4c0/12871_2022_1750_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/56fbaff13fa1/12871_2022_1750_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e325/9290278/756ca9f72e91/12871_2022_1750_Fig5_HTML.jpg

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