中药药理与临床2025，Vol.41Issue(11)：2-9,8.
当归芍药散不同剂型改善东莨菪碱诱导小鼠认知障碍的作用机制研究
Mechanisms of Different Dosage Forms of Danggui Shaoyao Powder in Ameliorating Scopolamine-Induced Cognitive Impairment in Mice
摘要
Abstract
Objective:To investigate the specific effects of different dosage forms of Danggui Shaoyao Powder(当归芍药散)on scopolamine(SCOP)-induced cognitive impairment in mice and to explore its potential underlying mechanisms.Methods:C57BL/6J mice were randomly divided into normal control group,model control group,Danggui Shaoyao Powder groups of different dosage forms(decoction group,powder group,and granule group,each at 6.4 mg/kg),and the donepezil hydrochloride group(3 mg/kg).After six weeks of administration,all groups except the normal control group received intraperitoneal injections of SCOP to induce the model.Thirty minutes after modeling,the Morris water maze,Y-maze,open field test,and novel object recognition test were conducted to evaluate cognitive and behavioral changes.Ser-um lipid metabolism-related indices were assessed to evaluate metabolic function.Nissl staining and hematoxylin-eosin(HE)staining were used for histopathological analysis of brain tissue.At the biochemical level,indicators related to cholinergic function and oxidative stress in brain tissue were measured.The mRNA expression levels of synaptophysin(Syn),brain-derived neurotrophic factor(Bdnf),nerve growth factor(Ngf),tight junction protein 1(Zo1),Claudin5,and Occludin in the hippocampus were detected by RT-qPCR.Protein expression lev-els of AMPK,mTOR,and their phosphorylated forms(p-AMPK,p-mTOR)in the hippocampus were analyzed by Western blot.Results:Com-pared with the normal control group,the model control group exhibited significant impairments in learning and memory functions(P<0.05 or P<0.01),a marked reduction in hippocampal neuron count(P<0.01),significant changes in oxidative stress and cholinergic system-related indicators(P<0.05 or P<0.01),slower blood glucose decline with faster recovery,and significant downregulation of Bdnf,Ngf,Syn,Occlu-din,Claudin5,and Zo1 mRNA expression(P<0.05 or P<0.01).The expression of p-AMPK protein and relative fluorescence quantification were reduced,and p-mTOR protein expression was significantly downregulated(P<0.05 or P<0.01).Compared with the model control group,mice in all Danggui Shaoyao Powder treatment groups showed improved learning and memory performance(P<0.05 or P<0.01).Nissl and HE staining indicated alleviated hippocampal neuronal damage.Blood glucose levels decreased,serum levels of triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were reduced,and high-density lipoprotein cholesterol(HDL-C)levels increased(P<0.05 or P<0.01).In hippocampal tissues,levels of reactive oxygen species(ROS),malondialdehyde(MDA),and acetylcholinesterase(AChE)were decreased(P<0.05 or P<0.01),while levels of superoxide dismutase(SOD),acetylcholine(ACh),and choline acetyltransferase(ChAT)were significantly elevated(P<0.01).The mRNA expression levels of Bdnf,Ngf,Syn,Occludin,Claudin5,and Zo1 were signifi-cantly upregulated(P<0.05 or P<0.01),p-AMPK protein expression and relative fluorescence intensity were increased,and p-mTOR protein expression was also significantly upregulated (P<0. 05 or P<0. 01). Conclusion:Danggui Shaoyao Powder in the forms of decoction,powder,and granules can all improve SCOP-induced cognitive impairment in mice,with no significant difference in efficacy among the dosage forms.The mechanism may be related to the activation of the AMPK/mTOR signaling pathway,which improves disordered energy metabolism in thebrain,restores cholinergic system function,alleviates oxidative stress damage,promotes synaptic protein expression,and ultimately reducesneuronal apoptosis.关键词
当归芍药散/剂型/阿尔茨海默病/认知障碍/腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白Key words
Danggui Shaoyao Powder/Dosage form/Alzheimer's disease/Cognitive impairment/AMPK/mTOR引用本文复制引用
丁海霞,杨从,王奇,陈秀如,罗柏榤,苏世杰,蔡晗,林蕾洁,林东新,王玉婷,刘壮壮..当归芍药散不同剂型改善东莨菪碱诱导小鼠认知障碍的作用机制研究[J].中药药理与临床,2025,41(11):2-9,8.基金项目
国家自然科学基金面上项目(编号:82274616) （编号:82274616）
广东省基础与应用基础研究基金企业联合基金(编号:2022A1515220121). （编号:2022A1515220121）
