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

被引:52
作者
Chen, Lin [1 ]
Xie, Wenji [2 ]
Xie, Wenqin [2 ]
Zhuang, Weiqiang [1 ]
Jiang, Changcheng [2 ]
Liu, Naizhen [2 ]
机构
[1] Huian Hosp, Dept Anesthesiol, 182 Zhongshan North Rd, Quanzhou 362000, Peoples R China
[2] Quanzhou First Hosp, Dept Anesthesiol, 248-252 Dong Rd, Quanzhou 362000, Peoples R China
关键词
Post operational cognitive dysfunction; Anesthesia; Isoflurane; Apigenin; Aged; HISTONE ACETYLATION; BDNF GENE; MEMORY; IMPAIRMENTS; ANESTHESIA; PROMOTERS; DISEASE; INVOLVEMENT; EXPOSURE; DECLINE;
D O I
10.1016/j.archger.2017.07.004
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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 NF kappa B 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.
引用
收藏
页码:29 / 36
页数:8
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