实用临床医药杂志2025，Vol.29Issue(12)：6-12,7.DOI:10.7619/jcmp.20246474
环泊酚对帕金森病大鼠的保护作用及调控机制研究
Protective effect and regulatory mechanism of ciprofol for rats with Parkinson's disease
摘要
Abstract
Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.关键词
环泊酚/帕金森病/腺苷酸活化蛋白激酶/沉默信息调节因子1/自噬/运动功能/认知功能/过氧化物酶体增殖物激活受体γ共激活因子1αKey words
ciprofol/Parkinson's disease/adenosine monophosphate-activated protein ki-nase/silent information regulator 1/autophagy/motor function/cognitive function/peroxisome pro-liferator-activated receptor gamma coactivator 1α分类
医药卫生引用本文复制引用
张亚飞,刘宇芳,汤燕彬,廖兴志..环泊酚对帕金森病大鼠的保护作用及调控机制研究[J].实用临床医药杂志,2025,29(12):6-12,7.基金项目
江苏省无锡市"双百"中青年医疗卫生拔尖人才培养计划项目(BJ2023110) （BJ2023110）
中国人民解放军联勤保障部队第904医院2023年度医院自主科研项目(ZZ202304) （ZZ202304）
