中国实验方剂学杂志2026，Vol.32Issue(19)：79-88,10.DOI:10.13422/j.cnki.syfjx.20260631
开玄解毒核心方通过调控HPA轴与神经炎症缓解束缚应激加重的IMQ诱导银屑病样皮损
Kaixuan Jiedu Core Prescription Alleviates Restraint Stress-exacerbated Imiquimod-induced Psoriasis-like Skin Lesions via Regulation of HPA Axis and Neuroinflammation
摘要
Abstract
Objective:To investigate the ameliorative effect and potential mechanisms of Kaixuan Jiedu core prescription(KXJD)on imiquimod(IMQ)-combined restraint stress-induced psoriasis-like skin lesions in mice.Methods:A total of 36 C57BL/6J mice were randomly assigned to six groups(n=6 per group):Normal group,restraint stress blank group,model group,restraint stress model group,KXJD group(30.42 g·kg-1),and methotrexate group(0.001 g·kg-1).Psoriasis-like lesions were induced by topical IMQ application combined with restraint stress.After 5 days of intervention,the severity of skin lesions was evaluated using the Psoriasis Area and Severity Index(PASI).The following parameters were assessed:Hypothalamic-pituitary-adrenal(HPA)axis-related hormones,including adrenocorticotropic hormone(ACTH),corticotropin-releasing hormone(CRH),and corticosterone(CORT),central neuronal markers,including neuronal nuclei antigen(NeuN),microtubule-associated protein 2(MAP2),and beta Ⅲ-tubulin(β-Ⅲ tubulin),microglial activation markers,including ionized calcium-binding adapter molecule-1(Iba-1)and cluster of differentiation 11b(CD11b),and skin nerve fiber markers,including protein gene product 9.5(PGP9.5)and serotonin(5-HT),as well as the expression levels of inflammatory cytokines tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-1 beta(IL-1β).Results:Compared with the normal group,both the model group and the restraint stress model group exhibited more severe psoriasis-like skin lesions,with significantly elevated serum levels of ACTH,CRH,and CORT(P<0.01).The expression of glucocorticoid receptor(GR)and corticotropin-releasing hormone receptor 1(CRHR1)in the skin was significantly downregulated.The expression of NeuN,MAP2,β-Ⅲ tubulin,Iba-1,and CD11b in the hypothalamus and hippocampus was significantly upregulated,suggesting abnormal changes in neuronal number or structure and aberrant activation of glial cells(P<0.05,P<0.01).In addition,the expression of PGP9.5 and 5-HT in the skin,as well as the mRNA levels of TNF-α,IL-6,and IL-1β were all markedly elevated(P<0.05,P<0.01).Compared with the model group,the restraint stress model group showed further exacerbation in most parameters.Compared with the restraint stress model group,the KXJD group exhibited significantly reduced PASI scores(P<0.01),significantly decreased serum CRH,ACTH,and CORT levels(P<0.05,P<0.01),upregulated skin GR and CRHR1 expression,inhibited abnormal neuronal changes and microglial activation in the hypothalamus and hippocampus,attenuated skin nerve fiber hyperplasia and amine signaling molecule release,and significantly reduced pro-inflammatory cytokine mRNA expression(P<0.05,P<0.01).Conclusion:Kaixuan Jiedu Core prescription can effectively ameliorate IMQ combined with restraint stress-induced psoriasis-like skin lesions in mice by modulating HPA axis function,inhibiting central neuropathological changes,and attenuating skin nerve fiber hyperplasia,amine signaling molecule(5-HT)release and local inflammatory responses.关键词
开玄解毒核心方/银屑病/束缚应激/下丘脑-垂体-肾上腺轴/炎症Key words
Kaixuan Jiedu core prescription(KXJD)/psoriasis/restraint stress/hypothalamic-pituitary-adrenal axis/inflammation分类
医药卫生引用本文复制引用
张宁馨,杨昊若,李佳琦,江梦瑶,吴嘉荣,刘欣茜,杨斌,宋坪..开玄解毒核心方通过调控HPA轴与神经炎症缓解束缚应激加重的IMQ诱导银屑病样皮损[J].中国实验方剂学杂志,2026,32(19):79-88,10.基金项目
国家自然科学基金面上项目(82474521) （82474521）
北京市高层次创新创业人才支持计划"登峰、青苗、春蕾"项目(G202514020) （G202514020）
