中国病理生理杂志2024，Vol.40Issue(5)：827-835,9.DOI:10.3969/j.issn.1000-4718.2024.05.007
SIRT3激动剂厚朴酚通过抑制海马神经元铁死亡缓解小鼠术后认知功能障碍
Honokiol,an SIRT3 activator,alleviates postoperative cognitive dysfunc-tion via inhibiting hippocampal neuronal ferroptosis in mice
摘要
Abstract
AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.关键词
厚朴酚/术后认知功能障碍/铁死亡/沉默信息调节因子3Key words
honokiol/postoperative cognitive dysfunction/ferroptosis/silent information regulator 3分类
医药卫生引用本文复制引用
黄涛,韩甜甜,许倩倩,张振,胡鹏超,丁旭东,罗辉宇,曾炼..SIRT3激动剂厚朴酚通过抑制海马神经元铁死亡缓解小鼠术后认知功能障碍[J].中国病理生理杂志,2024,40(5):827-835,9.基金项目
湖北省教育厅科研计划重点项目(No.D20212103) （No.D20212103）
湖北省卫健委项目(No.WJ2023F077 （）
No.WJ2023F078) （）
襄阳市科技局项目(No.2022YL29A （）
No.2022YL24B （）
No.2021YL123 （）
No.2021ZD12) （）
湖北医药学院研究生创新项目(No.YC2022048) （No.YC2022048）
襄阳市第一人民医院科技创新项目(No.XYY2023SD05 （）
No.XYY2023SD21 （）
No.XYY2023QT12) （）
