摘要
目的 通过细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)/环磷酸腺苷反应元件结合蛋白(cyclic adenosine monophosphate response binding protein,CREB)/脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)信号通路及肠道菌群探究滋水清肝饮对慢性束缚应激制备的小鼠抑郁模型的干预作用。方法 除对照组外,建立慢性束缚应激模型,造模21 d后根据糖水偏好实验结果随机分成模型组、盐酸氟西汀(0.01 g/kg)组和滋水清肝饮低、中、高剂量(8.835、17.670、35.340 g/kg)组。每周给药结束后进行糖水偏好实验及行为学实验。苏木素-伊红(HE)染色观察小鼠全脑及结肠病理变化;免疫荧光染色检测海马小胶质细胞标志物离子钙结合衔接分子-1(ionized calcium binding adapter molecule-1,Iba-1)荧光强度;检测小鼠血清中超氧化物歧化酶(superoxide dismutase)活性及丙二醛(malondialdehyde,MDA)、5-羟色胺(5-hydroxytryptamine,5-HT)、促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、促肾上腺皮质激素释放激素(corticotropin releasing hormone,CRH)、皮质酮(corticosterone,CORT)水平;检测小鼠前额叶皮层中SOD活性及BDNF、5-HT、MDA水平;通过16S rRNA基因测序检测小鼠结肠肠道内容物的组成和结构;检测小鼠前额叶皮层组织中ERK1/2、p-ERK1/2、CREB、p-CREB、BDNF蛋白表达。结果 与模型组比较,滋水清肝饮组小鼠糖水偏好率显著升高(P<0.01),悬尾实验和强迫游泳实验不动时间显著缩短(P<0.05、0.01),血清中MDA及ACTH、CRH及CORT含量降低(P<0.05、0.01),SOD活性及5-HT含量升高(P<0.05、0.01);前额叶皮层中BDNF、5-HT含量及SOD活性增加(P<0.05、0.01),MDA含量降低(P<0.01);海马CA1区、皮层及结肠组织中病理情况改善,海马中CA1区Iba-1荧光强度减弱;各给药组肠道菌群中益生菌拟杆菌门、放线菌门、杜氏杆菌属、乳杆菌属、毛螺菌属等丰度增加,有害菌厚壁菌门、变形杆菌门�
Objective To investigate the intervention effect of Zishui Qinggan Yin(滋水清肝饮) on depression model of mice prepared by chronic restraint stress through extracellular regulated protein kinase(ERK)/cyclic adenosine monophosphate response binding protein(CREB)/brain-derived neurotrophic factor(BDNF) signaling pathway and gut microbiota.Methods Except the control group,other mice were induced to establish the chronic restraint stress model.After 21 d of modeling,mice were randomly divided into model group,fluoxetine hydrochloride(0.01 g/kg) group,Zishui Qinggan Yin low-,medium-and high-dose(8.835,17.67,35.34 g/kg) groups according to the results of sucrose preference test.The sucrose preference test and behavioral test were conducted after weekly administration.Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the whole brain and colon of mice.The fluorescence intensity of ionized calcium binding adapter molecule-1(Iba-1),a marker of microglia cells in hippocampus,was determined by immunofluorescence staining.Superoxide dismutase(SOD) activity,malonaldehyde(MDA),5-hydroxytryptamine(5-HT),adrenocorticotropic hormone(ACTH),corticotropin releasing hormone(CRH) and corticosterone(CORT)levels in serum were detected.BDNF,5-HT,MDA levels and SOD activity in frontal cortex of mice were detected.The composition and structure of gut microbiota in colon of mice were examined by 16S rRNA gene sequencing.The expressions of ERK1/2,p-ERK1/2,CREB,p-CREB and BDNF in prefrontal cortex tissue of mice were detected.Results Compared with model group,sucrose preference rate of mice in Zishui Qinggan Yin group was increased(P < 0.01),immobility time of tail suspension experiment and forced swimming experiment weas significantly shortened(P < 0.05,0.01),the contents of MDA,ACTH,CRH and CORT in serum were decreased(P < 0.05,0.01),SOD activity and 5-HT content were increased(P < 0.05,0.01);The contents of BDNF,5-HT and SOD activity were increased in prefrontal cortex of mice(P < 0.05,0.01),the content of
作者
曹珊珊
史磊磊
张雨涵
史永恒
韩朝军
王斌
刘继平
CAO Shanshan;SHI Leilei;ZHANG Yuhan;SHI Yongheng;HAN Chaojun;WANG Bin;LIU Jiping(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China)
出处
《中草药》
CAS
CSCD
北大核心
2024年第2期489-498,共10页
Chinese Traditional and Herbal Drugs
基金
陕西省中医药管理局科研项目(2021-ZZ-JC003)
陕西省教育厅专项科研计划项目(21JK0607)
陕西省自然科学基础研究计划项目(2022JQ-918)
陕西省陕西中医药大学校级科研课题项目(2021GP25)。
