Astragaloside Ⅳ protects against rat cerebral ischemia-reperfusion inju-ry via PINK1/parkin mitophagy-associated pathway
10.3969/j.issn.1000-4718.2025.03.010
- VernacularTitle: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
- Author:
Li MA
1
;
Junjie ZHAO
;
Peng WANG
;
Jianhua QIAN
;
Liangyong LI
Author Information
1. 安徽中医药大学中西医结合学院,安徽 合肥 230001
- Publication Type:Journal Article
- Keywords:
astragaloside Ⅳ;
mitophagy;
oxidative stress;
cerebral ischemia-reperfusion injury
- From:
Chinese Journal of Pathophysiology
2025;41(3):501-508
- CountryChina
- Language:Chinese
-
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.
