针刺研究2025，Vol.50Issue(11)：1238-1247,10.DOI:10.13702/j.1000-0607.20240883
基于cGAS-STING信号通路介导的铁自噬探讨电针对大脑中动脉闭塞大鼠学习记忆障碍的影响
Exploring the effect of electroacupuncture on learning and memory impairment in rats with middle cerebral artery occlusion through ferritinophagy mediated by cGAS-STING signaling pathway
摘要
Abstract
Objective To observe the effect of electroacupuncture(EA)on learning and memory in rats with middle cerebral artery occlusion/reperfusion(MCAO/R)by regulating ferritinophagy through the cyclic GMP-adenosine synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods SD rats were randomly divided into a normal group,a model group,and an EA group.Except for the normal group,all rats underwent MCAO/R by suture occlusion.The EA group received treatment at"Shenting"(GV24)and"Baihui"(GV20)for 30 min once daily for 14 d.The Zea-Longa score was used to assess neurological deficits in rats.The Morris water maze test and the new object recognition test were used to evaluate the learning and memory abilities of rats.The elevated plus maze test was used to evaluate the anxiety state of rats.The TTC staining was used to measure the infarct volume of rats.The HE staining method was used to observe pathological changes in rat's brain tissue.Iron deposition in the hippocampus was assessed with Prussian blue staining.Mitochondrial morphology in the hippocampus of rats was observed using transmission electron microscopy.Western blot was used to detect the protein expression levels of cGAS,STING,nuclear receptor coactivator 4(NCOA4),ferritin heavy chain 1(FTH1),P62,Beclin1,and the ratio of micro tubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3Ⅰ in the hippocampus of rats.Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of interferon regulatory factor 3(IRF3),TANK-binding kinase 1(TBK1),Interleukin-10(IL-10),Interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the hippocampus of rats.Results Compared with the normal group,the neurological deficit scores,infarct volume,escape latency,time to explore old objects,and the expression levels of cGAS,STING,NCOA4,Beclin1,and the ratio of LC3Ⅱ/LC3Ⅰproteins,as well as IRF3,TBK1,IL-1β,and TNF-α mRNAs were increased(P<0.01)in the model group;the number of times crossing the original platform,the time spent exploring new objects,cognitive index,the percentage of time spent in the open arms,the percentage of times spent in the open arms,and the expression levels of FTH1,P62 proteins,and IL-10 mRNA were decreased(P<0.01).The model group displayed sparse hippocampal CA1 neurons,fewer cells,disorganized structure,and evident brownish iron deposition.Mitochondria appeared swollen with disrupted cristae.Compared with the model group,the EA group showed reduced neurological deficit scores,infarct volume,escape latency,time to explore old objects,and the expression levels of cGAS,STING,NCOA4,Beclin1,and the ratio of LC3Ⅱ/LC3Ⅰ,IRF3,TBK1,IL-1β,and TNF-α mRNAs(P<0.05,P<0.01).Meanwhile,the number of times crossing the original platform,the time spent exploring new objects,cognitive index,the percentage of time spent in the open arms,the percentage of times spent in the open arms,and the expression levels of FTH1,P62 proteins,and IL-10 mRNA increased in the EA group(P<0.01,P<0.05).The EA group showed improved neuronal arrangement in the hippocampal CA1,with uniform cell spacing and more regular cell morphology.Iron deposition was reduced.Mitochondria demonstrated improved morphology,with less cristae dissolution but no obvious rupture,appearing more normal and structurally intact.Conclusion EA can improve the learning and memory abilities of MCAO/R rats,and its mechanism may be related to the inhibition of ferritinophagy mediated by the cGAS-STING signaling pathway.关键词
缺血性脑卒中/电针/环磷酸鸟苷-腺苷合成酶/干扰素基因刺激因子信号通路/铁自噬Key words
Ischemic stroke/Electroacupuncture/cGAS-STING signaling pathway/Ferritinophagy引用本文复制引用
王亚敏,吕转,于浩冉,高静,陈立典,冯晓东..基于cGAS-STING信号通路介导的铁自噬探讨电针对大脑中动脉闭塞大鼠学习记忆障碍的影响[J].针刺研究,2025,50(11):1238-1247,10.基金项目
国家自然科学基金项目(No.82174473) （No.82174473）
河南中医药大学研究生科研创新项目(No.2023KYCX014) （No.2023KYCX014）
