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芹菜素通过表观遗传调控和神经炎症减轻老年大鼠异氟烷诱导的认知功能障碍。

Apigenin attenuates isoflurane-induced cognitive dysfunction via epigenetic regulation and neuroinflammation in aged rats.

作者信息

Chen Lin, Xie Wenji, Xie Wenqin, Zhuang Weiqiang, Jiang Changcheng, Liu Naizhen

机构信息

Department of Anesthesiology, Hui'an Hospital, No. 182 Zhongshan North Road, Quanzhou 362000, China.

Department of Anesthesiology, Quanzhou First Hospital, No. 248-252 Dong Road, Quanzhou 362000, China.

出版信息

Arch Gerontol Geriatr. 2017 Nov;73:29-36. doi: 10.1016/j.archger.2017.07.004. Epub 2017 Jul 6.

DOI:10.1016/j.archger.2017.07.004
PMID:28743056
Abstract

PURPOSE OF THE RESEARCH

Post operational cognitive dysfunction (POCD) occurs in patients after anesthesia and surgery. Abnormal histone acetylation and neuroinflammation are key factors in the pathogenesis of cognitive impairment. Apigenin not only has an anti-inflammatory activity but also modifies histone acetylation. We aimed to investigate whether apigenin can attenuate isoflurane exposure-induced cognitive decline by regulating histone acetylation and inflammatory signaling.

MATERIALS AND METHODS

Spatial learning and memory were assessed by Morris water maze test. Levels of histone acetylation, BDNF and downstream signaling, and inflammatory components were analyzed.

PRINCIPAL RESULTS

Isoflurane exposure in aged rats lead to impaired spatial learning and memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation, which was accompanied by reduced BDNF expression and suppressed BDNF downstream signaling pathway. Apigenin restored histone acetylation and BDNF signaling. Apigenin also suppressed isoflurane exposure induced upregulation of proinflammatory cytokines and NFκB signaling pathway.

MAJOR CONCLUSIONS

Memory impairment induced by isoflurane exposure is associated with dysregulated histone acetylation in the hippocampus, which affects BDNF expression and hence BDNF downstream signaling pathway. Apigenin recovers cognitive function by restoring histone acetylation and suppressing neuroinflammation.

摘要

研究目的

术后认知功能障碍(POCD)发生于麻醉和手术后的患者。异常的组蛋白乙酰化和神经炎症是认知障碍发病机制中的关键因素。芹菜素不仅具有抗炎活性,还能修饰组蛋白乙酰化。我们旨在研究芹菜素是否能通过调节组蛋白乙酰化和炎症信号来减轻异氟烷暴露诱导的认知衰退。

材料与方法

通过莫里斯水迷宫试验评估空间学习和记忆。分析组蛋白乙酰化、脑源性神经营养因子(BDNF)及其下游信号以及炎症成分的水平。

主要结果

老年大鼠异氟烷暴露导致空间学习和记忆受损。这些大鼠表现出组蛋白H3K9和H4K12乙酰化失调,同时伴有BDNF表达降低和BDNF下游信号通路受抑制。芹菜素恢复了组蛋白乙酰化和BDNF信号。芹菜素还抑制了异氟烷暴露诱导的促炎细胞因子上调和NFκB信号通路。

主要结论

异氟烷暴露诱导的记忆障碍与海马体中组蛋白乙酰化失调有关,这影响了BDNF表达,进而影响BDNF下游信号通路。芹菜素通过恢复组蛋白乙酰化和抑制神经炎症来恢复认知功能。

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