中国病理生理杂志2025，Vol.41Issue(3)：501-508,8.DOI:10.3969/j.issn.1000-4718.2025.03.010
黄芪甲苷通过PINK1/parkin通路介导的线粒体自噬途径减轻大鼠脑缺血再灌注损伤
Astragaloside Ⅳ protects against rat cerebral ischemia-reperfusion inju-ry via PINK1/parkin mitophagy-associated pathway
摘要
Abstract
AIM:To clarify the molecular mechanism by which astragaloside Ⅳ(AS-Ⅳ)suppresses oxida-tive stress and alleviates cerebral ischemia-reperfusion injury(CIRI)via the PTEN-induced kinase 1(PINK1)/parkin mi-tophagy-associated pathway.METHODS:A middle cerebral artery occlusion/reperfusion(MCAO/R)model was estab-lished in Sprague-Dawley rats.The animals were allocated to sham,MCAO/R,AS-Ⅳ,and mitochondrial division inhibi-tor-1(Mdivi-1)treatment groups.The rats in AS-Ⅳ and Mdivi-1 groups were intraperitoneally injected once daily with AS-Ⅳ(20 mg/kg)for 7 d,while those in Midivi-1 group also received intraperitoneal injection of Mdivi-1(1.2 mg·kg-1·d-1).The rats in sham and MCAO/R groups were given equivalent volume of distilled water.Neurological deficits were as-sessed using Zea Longa scoring,infarcted area volumes were measured using TTC staining,and brain tissue pathology was examined using hematoxylin and eosin staining.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were assessed by ELISA,while those of reactive oxygen species(ROS)were measured using flow cytometry.The expres-sion levels of PINK1,parkin and microtubule-associated protein 1 light chain 3(LC3)were quantified using Western blot and RT-qPCR.RESULTS:AS-Ⅳ administration significantly alleviated neuronal and mitochondrial damage in MCAO/R model rat brains(P＜0.05),together with significant reductions in the cerebral infarct volume and neurological dysfunc-tion(P＜0.05).Significant increases in PINK1,parkin and LC3 protein and mRNA levels were observed in response to AS-Ⅳ(P＜0.05),SOD activity rose,and ROS and MDA levels declined significantly(P＜0.05).The co-administration of Mdivi-1 abrogated the protective benefits of AS-Ⅳ,inhibited activation of the PINK1/parkin pathway,down-regulated LC3 at the mRNA and protein levels,and significantly increased mitochondrial damage.Mdivi-1 also markedly reduced autophagosome formation and SOD activity level,but increased both ROS and MDA levels,cerebral infarct volume,and the severity of neurological deficits(P＜0.05).CONCLUSION:Astragaloside Ⅳ activates the PINK/parkin-mediated mitophagy pathway,inhibits oxidative stress and alleviates CIRI in rats.关键词
黄芪甲苷/线粒体自噬/氧化应激/脑缺血再灌注损伤Key words
astragaloside Ⅳ/mitophagy/oxidative stress/cerebral ischemia-reperfusion injury分类
临床医学引用本文复制引用
马莉,赵俊杰,王鹏,钱建华,李良勇..黄芪甲苷通过PINK1/parkin通路介导的线粒体自噬途径减轻大鼠脑缺血再灌注损伤[J].中国病理生理杂志,2025,41(3):501-508,8.基金项目
安徽省高等学校自然科学基金资助项目(No.2023AH050828 （）
No.2024AH050955) （）
安徽中医药大学人才支持计划项目(No.2023rcyb023) （No.2023rcyb023）
