中国中医药信息杂志2025，Vol.32Issue(6)：105-111,7.DOI:10.19879/j.cnki.1005-5304.202408203
基于HPA轴-MEK/ERK信号通路探讨柴胡加龙骨牡蛎汤治疗广泛性焦虑症大鼠的作用机制
Exploration on the Mechanism of Chaihu Longgu Muli Decoction in the Treatment of Generalized Anxiety Disorder Rats Based on the HPA Axis-MEK/ERK Signaling Pathway
摘要
Abstract
Objective To observe the effects of Chaihu Longgu Muli Decoction on oxidative stress in hippocampus and hypothalamic-pituitary-adrenal(HPA)axis hormone levels of rats with generalized anxiety disorder(GAD);To explore its mechanism of alleviating anxiety in GAD rats.Methods A total of 72 Wistar rats were randomly divided into blank group(12 rats)and modeling group(60 rats).Chronic restraint stress was used to establish the GAD model.The successfully modeled rats were randomly divided into model group,diazepam group(1 mg/kg)and TCM low-,medium-and high-dosage groups(Chaihu Longgu Muli Decoction 6,12,24 g/kg).The administration groups were given corresponding drugs by gavage for 14 consecutive days.Open field experiment and elevated cross maze experiment were used to observe indexes in rat behavior,HE staining was used to observe the morphology of hippocampal tissue,ELISA was used to detect the contents of serum corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH)and corticosterone(CORT),biochemical kits were used to detect the contents of malondialdehyde(MDA),catalase(CAT)and superoxide dismutase(SOD)in hippocampal tissue,RT-PCR was used to detect the mRNA expressions of MEK,ERK,Bax and Bcl-2 in hippocampal tissue,Western blot was used to detect the protein expressions of MEK,p-MEK,ERK,p-ERK,Bax and Bcl-2 in hippocampal tissue.Results Compared with the blank group,the rats in the model group had a significantly slower growth rate of body msss,loose stool,dark hair,significant hair removal and extreme agitation;the activity time and distance in the central area were significantly reduced(P<0.01),the percentage of time,frequency and distance of entering the open arm were significantly reduced(P<0.01);with structural degeneration of hippocampal neurons,changes in cell morphology,disordered arrangement and edema of surrounding tissues;the contents of serum CRH,ACTH and CORT significantly increased(P<0.01);the MDA content in hippocampal tissue significantly increased(P<0.01),CAT and SOD contents significantly decreased(P<0.01),p-MEK and p-ERK protein expressions significantly decreased(P<0.01),Bax mRNA and protein expressions significantly increased(P<0.01),Bcl-2 mRNA and protein expressions significantly decreased(P<0.01).Compared with the model group,the body mass growth rate of diazepam group and each dosage of TCM group increased,and the symptoms of loose stool,hair removal,anxiety and huddling were improved;the activity time and distance in the central area of rats in the diazepam group and TCM medium-and high-dosage groups significantly increased(P<0.01),and the percentage of time,frequency and distance of entering the open arm significantly increased(P<0.05,P<0.01);the contents of serum CRH,ACTH and CORT significantly decreased(P<0.05,P<0.01);the MDA content in the hippocampal tissue in diazepam group and TCM high-dosage group significantly decreased(P<0.01),while the CAT and SOD contents significantly increased(P<0.05,P<0.01),the protein expressions of p-MEK and p-ERK in hippocampal tissue in diazepam group and TCM medium-and high-dosage group significantly decreased(P<0.01),Bax mRNA and protein expressions were significantly decreased(P<0.01),and Bcl-2 mRNA and protein expressions significantly increased(P<0.05,P<0.01).There was no statistical significance in the expressions of MEK,ERK mRNA and protein among the groups(P>0.05).Conclusion Chaihu Longgu Muli Decoction can alleviate anxiety in GAD rats by inhibiting HPA axis hormone release and MEK/ERK signaling pathway activation,improving neuroendocrine levels,and reducing hippocampal oxidative stress response.关键词
广泛性焦虑症/柴胡加龙骨牡蛎汤/下丘脑-垂体-肾上腺轴/MEK/ERK信号通路/氧化应激/大鼠Key words
generalized anxiety disorder/Chaihu Longgu Muli Decoction/hypothalamic-pituitary-adrenal axis/MEK/ERK signaling pathway/oxidative stress/rats分类
医药卫生引用本文复制引用
胡亦明,杨蕤,韦春昕,黄仕琦,谭国伟,李晓,安耀荣..基于HPA轴-MEK/ERK信号通路探讨柴胡加龙骨牡蛎汤治疗广泛性焦虑症大鼠的作用机制[J].中国中医药信息杂志,2025,32(6):105-111,7.基金项目
甘肃省自然科学基金(22JR11RA121) （22JR11RA121）
甘肃中医药大学中医学一级学科"岐黄英才"导师专项基金硕士研究生导师开放基金(3016190124) （3016190124）
