中药新药与临床药理2025，Vol.36Issue(12)：2072-2079,8.DOI:10.19378/j.issn.1003-9783.2025.12.007
橄榄苦苷调节AMPK/SIRT1/PGC-1α信号通路对脑缺血-再灌注大鼠神经损伤的影响
Effect of Oleuropein on Neuroinjury in Rats with Cerebral Ischemia-Reperfusion via Modulating the AMPK/SIRT1/PGC-1α Signaling Pathway
摘要
Abstract
Objective To investigate the effect of oleuropein on neuroinjury and the AMPK/SIRT1/PGC-1α signaling pathway in rats with cerebral ischemia-reperfusion(CI/R).Methods A CI/R rat model was established.Successfully modeled rats were randomly divided into four groups(n=18 per group):the model group,the low-dose oleuropein group,the high-dose oleuropein group,and the pathway inhibitor group.Intragastric administration of the respective drugs began on the day of successful modeling,once daily for 14 consecutive days.An additional 18 rats served as the normal control group.Neurological deficit scores were assessed.Oxidative stress levels were measured by ELISA.Pathological damage to brain tissue was examined by hematoxylin-eosin(HE)staining.Cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Neuronal apoptosis was detected by TUNEL staining.The protein expression levels of the AMPK/SIRT1/PGC-1α signaling pathway were measured by Western Blot.Results Compared with the control group,the model group exhibited disordered neuronal cell arrangement,reduced neuronal count,presence of necrosis,pyknotic and deeply stained nuclei,and severe perineuronal vacuolization.Neurological deficit scores,cerebral infarct volume,levels of ROS and MDA,the apoptosis rate,and the expression of C-Caspase-3,Caspase-3,and Bax were significantly increased(P＜0.05),while SOD activity and the expression of Bcl-2,p-AMPK/AMPK,SIRT1,and PGC-1α were decreased(P＜0.05).Compared with the model group,the low-dose and high-dose oleuropein groups and the pathway inhibitor group showed relatively orderly neuronal arrangement,a small reduction in cell count,accompanied by small areas of necrosis and mild nuclear pyknosis.Their neurological deficit scores,cerebral infarct volume,levels of ROS and MDA,the apoptosis rate,and the expression of C-Caspase-3,Caspase-3,and Bax were decreased(P＜0.05),while SOD activity and the expression of Bcl-2,p-AMPK/AMPK,SIRT1,and PGC-1α were increased(P＜0.05).Compared with the high-dose oleuropein group,the pathway inhibitor group exhibited more severe neuronal pathological damage,aggravated neuronal apoptosis,necrosis,and nuclear pyknosis,along with increased neurological deficit scores,cerebral infarct volume,levels of ROS and MDA,the apoptosis rate,and the expression of C-Caspase-3,Caspase-3,and Bax(P＜0.05),whereas SOD activity and the expression of Bcl-2,p-AMPK/AMPK,SIRT1,and PGC-1α were decreased(P＜0.05).Conclusion Oleuropein can alleviate neuroinjury in CI/R rats,and its mechanism of action is related to the activation of the AMPK/SIRT1/PGC-1α signaling pathway.关键词
橄榄苦苷/AMPK/SIRT1/PGC-1α信号通路/脑缺血-再灌注/神经损伤/大鼠Key words
oleuropein/AMPK/SIRT1/PGC-1α signaling pathway/cerebral ischemia-reperfusion/neuroinjury/rats分类
医药卫生引用本文复制引用
孟莉,刘丹,刘淑燕,许坤,董沙沙..橄榄苦苷调节AMPK/SIRT1/PGC-1α信号通路对脑缺血-再灌注大鼠神经损伤的影响[J].中药新药与临床药理,2025,36(12):2072-2079,8.基金项目
河北省医学科学研究课题计划项目(20240753). （20240753）
