南方医科大学学报2026,Vol.46Issue(6):1365-1373,9.DOI:10.12122/j.issn.1673-4254.2026.06.16
头顶一颗珠通过调节内质网自噬保护卒中后认知障碍大鼠的神经功能
Trillium tschonoskii Maxim saponin protects neurological function in rats with post-stroke cognitive impairment by promoting ER-phagy
摘要
Abstract
Objective To investigate the mechanism that mediates the neuroprotective effects of Trillium tschonoskii Maxim(TTM)against post-stroke cognitive impairment(PSCI)in rats.Methods Adult SD rats were randomized into Sham operation,PSCI model,TTM,rapamycin(an autophagy inducer),3-methyladenine(an autophagy inhibitor),and TTM+3-MA groups,and rat models of cognitive impairment were established using a modified thread occlusion method.Cognitive function of the rats was assessed using Morris water maze test.Histopathological changes,neuronal apoptosis,dendritic spines,and protein expressions of FAM134B,LC3,ATG5,P62,GRP78,Bax,Bcl-2,IL-10,IL-1β,and TNF-α were evaluated using HE,Nissl,TUNEL,Golgi staining,immunohistochemistry,immunofluorescence staining,and Western blotting.Results Compared with the sham-operated rats,the rat models of PSCI showed significantly prolonged escape latency,reduced target quadrant time and platform crossings,severe hippocampal damage,increased ATG5 and GRP78 expression,elevated apoptosis,increased IL-1β,TNF-α,Bax,GRP78,and P62 expressions,and decreased IL-10,Bcl-2,and LC3 expressions,with slightly increased FAM134B-LC3 and calnexin-LC3 co-localization.Compared with those in the model group,the rats receiving TTM treatment showed significantly shortened escape latency,increased target quadrant time and platform crossings,increased ATG5 and dendritic spines,decreased GRP78 expression,enhanced FAM134B-LC3 and calnexin-LC3 co-localization,reduced IL-1β,TNF-α,Bax,GRP78,and P62 expressions,and increased FAM134B,ATG5,LC3,IL-10,and Bcl-2 expressions;the rats treated with 3-MA showed the opposite changes.Conclusion Excessive ER stress is activated early after stroke,shifting from adaptive to pro-apoptotic signaling,with insufficient ER-phagy flux.TTM modulates ER-phagy,alleviates ERS,reduces neuroinflammation and apoptosis,protects dendritic spines,and improves cognitive function in rats with PSCI.关键词
头顶一颗珠/内质网自噬/卒中后认知障碍/神经保护Key words
Trillium tschonoskii Maxim saponin/ER-phagy/post-stroke cognitive impairment/neuroprotection引用本文复制引用
杨丹,赵方毓,何一多,朱红,刘昕,陈显兵..头顶一颗珠通过调节内质网自噬保护卒中后认知障碍大鼠的神经功能[J].南方医科大学学报,2026,46(6):1365-1373,9.基金项目
国家自然科学基金(82260821) (82260821)
研究生教育创新项目(MYK2023072) (MYK2023072)
湖北民族大学科研项目(XN2303) (XN2303)
风湿性疾病发生与干预湖北省重点实验室青年项目(OIR202407Q) Supported by National Natural Science Foundation of China(82260821). (OIR202407Q)