实用临床医药杂志2025，Vol.29Issue(8)：78-85,8.DOI:10.7619/jcmp.20245329
积雪草苷通过抑制大鼠短暂性脑缺血后过度自噬和细胞凋亡发挥神经保护作用
Neuroprotective effects of asiaticoside by inhibiting excessive autophagy and apoptosis after transient cerebral ischemia in rats
摘要
Abstract
Objective To explore the neuroprotective effects and mechanisms of asiaticoside(AS)in rats with transient cerebral ischemia.Methods One hundred male Sprague-Dawley(SD)rats were randomly divided into five groups:sham-operated(Sham)group,transient middle cerebral artery occlusion(tMCAO)group,and low-,medium-,and high-dose AS(AS-L,AS-M,AS-H)groups,with 20 rats in each group.Except for the Sham group,rats in the other four groups under-went tMCAO surgery.Rats in the AS-L,AS-M,and AS-H groups received intragastric administration of 20,40 and 80 mg/kg AS respectively,once daily for 7 days starting 1 hour post-surgery.Rats in the Sham and tMCAO groups received equivalent volumes of saline.Neurological deficit score,brain water content,and TTC staining were used to evaluate neurological impairment,cerebral edema,and infarct volume.HE staining and Nissl staining wereused to assess histopathological changes and neu-ronal damage.Autophagy was detected via transmission electron microscopy.Immunofluorescence staining was usedto analyze the expression and localization of microtubule-associated protein light chain 3B(LC3B).TUNEL staining was used to evaluate apoptosis,and Western blot was used to measure protein expression.Results Compared with the Sham group,rats in the tMCAO group ex-hibited significantly increased neurological deficit score,brain water content,infarct volume,and histopathological damage,as well as significantly decreased Nissl body counts(P＜0.05).AS dose-dependently reduced neurological deficits,brain water content,infarct volume,and histopatho-logical damage while increased Nissl body numbers.The tMCAO group showed significantly higher numbers of autophagosomes,lysosomes,and LC3B-positive cells,along with significantly elevated LC3-Ⅱ/LC3-Ⅰ,Beclin-1,Bax,cleaved caspase-3 compared to the Sham group;in contrast,p-PI3K,p-Akt,and p-mTOR protein levels,intact mitochondria count and p62 and Bcl-2 protein levels were significantly lower inthe tMCAO group(P＜0.05).Compared with the tMCAO group,AS treatment dose-dependently significantly decreased autophagosomes,lysosomes,LC3B-positive cells,and the expression of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,Bax,cleaved caspase-3 while significantly increased p-PI3K,p-Akt,and p-mTOR protein,intact mitochondria and p62 and Bcl-2 levels(P＜0.05).Conclusion AS exerts neuroprotective effects by inhibiting excessive autophagy and apopto-sis in rats with transient cerebral ischemia via activation of the PI3K/Akt/mTOR signaling pathway.关键词
积雪草苷/短暂性脑缺血/细胞自噬/细胞凋亡/短暂性大脑中动脉栓塞/微管相关蛋白轻链3B/哺乳动物雷帕霉素靶蛋白/内质网应激Key words
asiaticoside/transient cerebral ischemia/autophagy/apoptosis/transient mid-dle cerebral artery occlusion/microtubule-associated protein light chain 3B/mammalian target of ra-pamycin/endoplasmic reticulum stress分类
药学引用本文复制引用
石昆,窦岩,古庆柱,高居松,刘志强..积雪草苷通过抑制大鼠短暂性脑缺血后过度自噬和细胞凋亡发挥神经保护作用[J].实用临床医药杂志,2025,29(8):78-85,8.基金项目
河北省中医药管理局科研计划项目(2023279) （2023279）
