中国临床药理学杂志2024，Vol.40Issue(8)：1175-1179,5.DOI:10.13699/j.cnki.1001-6821.2024.08.018
胞磷胆碱对脑出血小鼠Keap1/Nrf2/ARE信号通路的影响
Effects of citicoline on Keap1/Nrf2/ARE signaling pathway in mice with cerebral hemorrhage
摘要
Abstract
Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.关键词
胞磷胆碱/Kelch样ECH关联蛋白1/核因子E2相关因子2/抗氧化反应元件信号通路/康复训练/神经保护Key words
citicoline/Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant response element signaling pathway/rehabilitation training/neuroprotection分类
医药卫生引用本文复制引用
卢苇,尤红,张敏,何宝峰,马瑞,高雅雅,马鑫宇..胞磷胆碱对脑出血小鼠Keap1/Nrf2/ARE信号通路的影响[J].中国临床药理学杂志,2024,40(8):1175-1179,5.基金项目
甘肃省自然科学基金资助项目(21JR1RA020,21JR7RA597) （21JR1RA020,21JR7RA597）
甘肃省人民医院院内基金资助项目(22GSSYD-65,22GSSYD-66,22GSSYB-9) （22GSSYD-65,22GSSYD-66,22GSSYB-9）
