中国免疫学杂志2025，Vol.41Issue(6)：1350-1357,8.DOI:10.3969/j.issn.1000-484X.2025.06.016
基于SIRT1研究HSYA激活神经元自噬保护脑缺血再灌注损伤
Study on protection of cerebral ischemia-reperfusion injury by HSYA activated neuronal autophagy based on SIRT1
摘要
Abstract
Objective:To investigate effect and mechanism of hydroxysafflor yellow A(HSYA)activating neuronal autophagy on cerebral ischemia-reperfusion injury through a combination of in vitro and in vivo experiments.Methods:SD rat MCAO/R model was established by improved suture method.Rats were randomly divided into sham surgery(Sham)group,MCAO/R group and MCAO/R+HSYA group,following indicators were detected to determine extent of cerebral ischemia-reperfusion nerve damage:Z-Longa neu-rological function score was detected,TTC staining to measure cerebral infarction area,and TUNEL staining to measure cell apopto-sis;Western blot was used to detect protein expressions of autophagy related markers LC3,Beclin1,P62 and SIRT1 in rat brain tis-sue;immunofluorescence staining was used to observe expression of LC3 co-localization with neurons.OGD/R injury model of SH-SY5Y cells was established and randomly divided into Normal group,OGD/R group,OGD/R+HSYA group,OGD/R+SIRT1 inhibitor(EX-527)group and OGD/R+EX-527+HSYA group.Western blot was used to detect protein expressions of LC3,Beclin1,P62 and SIRT1.Results:Compared with Sham group,model group rats showed impaired neurological function,significantly increased neu-robehavioral scores,widespread cerebral infarction,significantly increased neuronal cell apoptosis,significantly increased autophagy related protein Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,significantly decreased P62 expression,significantly increased LC3/NeuN co-stained cells,and decreased SIRT1 expression;compared with model group,HSYA intervention group showed a significant decrease in neurological functional scores,a significant reduction in cerebral infarction area,a significant decrease in neuronal cell apoptosis,a further increase in Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,a further decrease in P62 expression,number of LC3/NeuN and P62/NeuN co-stained cells also increased,and SIRT1 expression significantly increased.Expression trends of Beclin1,LC3-Ⅱ/LC3-Ⅰ,P62 and SIRT1 of cells between normal group,model group and HSYA intervention group were same as animal experiment;compared with model group,expressions of SIRT1,Beclin1 and LC3-Ⅱ/LC3-Ⅰ in OGD/R+EX-527 group were significantly reduced,while expression of P62 was significantly increased;compared with OGD/R+EX-527 group,there was no significant change in SIRT1 expression in OGD/R+EX-527+HSYA group,LC3-Ⅱ/LC3-Ⅰ and Beclin1 expression were significantly increased,and P62 expres-sion was significantly decreased.Conclusion:HSYA can significantly improve neurological deficits in rats after cerebral ischemia-reperfusion,reduce cerebral infarction area,and decrease neuronal cell apoptosis rate,whose neuroprotective effect may be related to its activation of SIRT1,which significantly enhances neuronal autophagy.关键词
羟基红花黄色素A/神经元自噬/SIRT1/脑缺血再灌注损伤Key words
Hydroxysaffron yellow A/Neuronal autophagy/SIRT1/Cerebral ischemia-reperfusion injury分类
中医学引用本文复制引用
宋丽娟,肖保国,马存根,魏汝恒,戴瑶瑶,滑键林,戎梦玮,但存燕,温春丽,夏天晴,张策..基于SIRT1研究HSYA激活神经元自噬保护脑缺血再灌注损伤[J].中国免疫学杂志,2025,41(6):1350-1357,8.基金项目
国家自然科学基金青年科学基金项目(82004028) （82004028）
中国博士后科学基金面上项目(2020M680912) （2020M680912）
国家中医药管理局"张仲景传承与创新专项"(GZY-KJS-2022-048-1) （GZY-KJS-2022-048-1）
山西省科技创新人才青年团队项目(202204051001028) （202204051001028）
山西省科技合作交流专项(202304041101004) （202304041101004）
山西省卫健委医学科技领军团队项目(2020TD05) （2020TD05）
山西中医药大学学科建设经费(2024XKJS-02) （2024XKJS-02）
山西中医药大学科技创新能力培育计划国家自然科学基金培育专项(2024PY-NS-012). （2024PY-NS-012）
