天津中医药大学学报2026,Vol.45Issue(7):804-811,8.DOI:10.11656/j.issn.1673-9043.2026.07.07
山柰酚调控Wnt/β-catenin信号通路对急性缺血性脑卒中大鼠的保护作用研究
Protective effect of kaempferol on rats with acute ischemic stroke by regulating Wnt/β-catenin signaling pathway
摘要
Abstract
[Objective]To explore the effects of kaempferol on neurological function,inflammation,cerebral infarction volume and pathological damage of brain tissue in rats with acute ischemic stroke(AIS),and analyze whether the regulatory effect on the wingless MMTV integration site family(Wnt)/β-catenin signaling pathway is its mechanism of action.[Methods]The rat model of AIS was established by middle cerebral artery embolization and reperfusion.The 72 successfully modeled AIS rats were randomly divided into model group,kaempferol group(50 mg/kg),Wnt/β-catenin pathway inhibitor group(ICG-001,5 mg/kg),kaempferol+Wnt/β-catenin pathway inhibitor group(50 mg/kg+5 mg/kg),with 18 rats in each group.Another 18 rats were selected as the sham operation group(performing the same surgical operations without inserting the suture plugs).Each group received corresponding intervention for 14 days.The neurological function impairment of rats was evaluated by the Zea-Longa score;the levels of serum inflammatory factors[tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),NOD-like receptor thermal protein domain-associated protein 3(NLRP3),interleukin-1β(IL-1β)]were determined by enzyme-linked immunosorbent assay;2,3,5-triphenyltetrazolium chloride staining was used to determine the percentage of cerebral infarction volume in rats;hematoxylin-eosin staining was used to observe the pathological changes of brain tissue in the ischemic cortical area of rats;the expressions of Wnt1,Wnt3a,β-catenin messenger RNA(mRNA)and protein in the brain tissue of the ischemic cortical area of rats were determined by fluorescence quantitative PCR and Western blotting,respectively.[Results]After 14 days administration,compared with sham operation group,the neuronal nuclei in the brain tissue of the ischemic cortical area of rats in model group were deformed and constricted,the arrangement was looser,the cells were polygonal,and necrotic cells could be seen,the neurological function impairment score,the levels of serum TNF-α,MCP-1,NLRP3,IL-1β,and the percentage of cerebral infarction volume were significantly increased,the Wnt1,Wnt3a,β-catenin mRNA and protein expression levels in the brain tissue of the ischemic cortical area were significantly decreased(P<0.05).Compared with model group,the phenomena of neuronal nucleus deformation and condensation,loose arrangement and cell necrosis in the brain tissue of the ischemic cortical area of rats in kaempferol group were significantly improved,the neurological function impairment score,the levels of serum TNF-α,MCP-1,NLRP3,IL-1β,and the percentage of cerebral infarction volume were significantly decreased,the Wnt1,Wnt3a,β-catenin mRNA and protein expression levels in the brain tissue of the ischemic cortical area were significantly increased(P<0.05);in the Wnt/β-catenin pathway inhibitor group,the phenomena of neuronal nucleus deformation and condensation,loose arrangement and cell necrosis in the brain tissue of the ischemic cortical area of rats were aggravated,the neurological function impairment score,the levels of serum TNF-α,MCP-1,NLRP3,IL-1β,and the percentage of cerebral infarction volume were significantly increased,the Wnt1,Wnt3a,β-catenin mRNA and protein expression levels in the brain tissue of the ischemic cortical area were significantly decreased(P<0.05).The pathological damage of brain tissue in the ischemic cortical area and the above quantitative indicators of rats in the kaempferol+Wnt/β-catenin pathway inhibitor group were worse than those in the kaempferol group and better than those in the Wnt/β-catenin pathway inhibitor group(P<0.05).[Conclusion]The activation effect on the Wnt/β-catenin signaling pathway may be the mechanism by which kaempferol improves neurological function,inflammation,cerebral infarction volume and pathological damage of brain tissue in AIS rats.关键词
山柰酚/急性缺血性脑卒中/神经功能/炎症/无翅型MMTV整合位点家族/β-连环蛋白Key words
kaempferol/acute ischemic stroke/neurological function/inflammation/wingless MMTV integration site family/β-catenin分类
医药卫生引用本文复制引用
李向男,杨松涛,李林,张志勇,李建民,张云鹤,李蕊..山柰酚调控Wnt/β-catenin信号通路对急性缺血性脑卒中大鼠的保护作用研究[J].天津中医药大学学报,2026,45(7):804-811,8.基金项目
河北省医学科学研究课题计划项目(20240045). (20240045)