摘要
目的:通过酪氨酸激酶2(JAK2)/细胞外调节蛋白激酶1/2(ERK1/2)/信号转导和转录激活因子3(STAT3)信号通路探究滋水清肝饮对皮质酮(CORT)代替饮水小鼠抑郁模型的干预作用。方法:除正常对照组外,用皮质酮代替饮水建立抑郁模型,造模21 d后根据糖水偏好结果随机分为模型对照组、盐酸氟西汀0.01 g/kg组、滋水清肝饮8.84、17.67、35.34 g/kg组,各组分别灌胃给药14 d。每周给药结束后进行糖水偏好试验及行为学试验,HE染色观察小鼠海马形态学改变;免疫荧光染色检测小鼠海马小胶质细胞标志物离子钙结合衔接分子-1(Iba-1)荧光强度,并统计其数量;检测小鼠血清和海马中丙二醛(MDA)、5-羟色胺(5-HT)、去甲肾上腺素(NA)、CORT含量;qRT-PCR法检测小鼠海马组织中肿瘤坏死因子-α(Tnfα)、白细胞介素1β(Il1b)mRNA的表达;Western blot法检测小鼠海马组织JAK2、p-JAK2、ERK1/2、p-ERK1/2、STAT3和p-STAT3蛋白的表达。结果:与正常对照组相比,模型对照组小鼠糖水偏好率降低;小鼠不动时间延长,运动路程、运动时间和平均速度降低,在边缘区域停留时间增加(P<0.05或P<0.01),海马神经细胞变形,轮廓模糊;海马DG区Iba-1荧光强度增强,数量增加,血清和海马中的5-HT和NA含量降低,MDA和CORT含量升高,小鼠海马Tnfα、Il1b mRNA表达上调,p-JAK2和p-STAT3蛋白表达上调,p-ERK1/2蛋白表达下调(P<0.05或P<0.01);与模型对照组相比,给药各组小鼠糖水偏好率提高,小鼠的不动时间缩短,运动路程、运动时间和平均速度明显增加,在边缘区域的停留时间明显降低(P<0.05或P<0.01),神经细胞改善,形态基本恢复正常;海马DG区Iba-1荧光强度降低,数量减少;血清和海马中的5-HT和NA含量升高,MDA和CORT含量降低;小鼠海马Tnfα、Il1b mRNA表达下调,p-JAK2和p-STAT3蛋白表达下调,p-ERK1/2蛋白表达上调,其中以滋水清肝饮17.67 g/kg组最为明显(P<0.05或P<0.01)。结论:滋水清肝饮能�
Objective:To investigate the intervention effect of Zishui Qinggan(滋水清肝)Decoction on the depression model of mice with corticosterone(CORT)replacing drinking water through the Januskinase 2(JAK2)/Extracellular regulated kinase 1/2(ERK1/2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Except for the normal control group,CORT was used to replace drinking water to establish a depression model of mice.After 21 days of modeling,the mice were randomly divided into five groups according to the sucrose preference results:model group,fluoxetine hydrochloride group(0.01 g/kg),and Zishui Qinggan Decoction groups(8.84 g/kg,17.67 g/kg and 35.34 g/kg).Fluoxetine hydrochloride and Zishui Qinggan Decoction groups were administrated intragastricly for 14 days,respectively.The sucrose preference test and the behavioral test were performed after weekly administration.The hematoxylin-eosin(HE)staining was used to observe the morphological changes in the hippocampus of mice.The fluorescence intensity of ionized calcium binding adapter molecule-1(Iba-1)was detected by immunofluorescence staining,and its quantity was counted.The contents of malonaldehyde(MDA),5-hydroxytryptamine(5-HT),noradrenaline(NA),and CORT in the serum and hippocampus of mice were detected.The mRNA expressions of tumor necrosis factor-α(Tnf-α)and Interleukin 1β(Il1β)in hippocampus of mice were determined by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),and the protein expressions of JAK2,p-JAK2,ERK1/2,p-ERK1/2,STAT3,and p-STAT3 in hippocampus of mice were determined by Western blotting(WB).Results:Compared with the normal control group,the sucrose preference rate of the model control group decreased,and the immobility time was prolonged.The movement distance,movement time,and average speed decreased,and the peripheral dwell time was prolonged.The nerve cells in the hippocampus were deformed and blurred in outline.The fluorescence intensity and quantity of Iba-1 in the DG region of the hippoc
作者
张雨涵
曹珊珊
史磊磊
张佳萍
史永恒
王斌
韩朝军
刘继平
ZHANG Yuhan;CAO Shanshan;SHI Leilei;ZHANG Jiaping;SHI Yongheng;WANG Bin;HAN Chaojun;LIU Jiping(Department of Pharmacology,Shaanxi University of Chinese Medicine,Xianyang 712046;Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine,Xianyang 712046;Shaanxi Key Laboratory for Safety Monitoring of Food and Drug,Xianyang 712046;Engineering Research Center of Brain Health Industry of Chinese Medicine,Universities of Shaanxi Province,Xianyang 712046)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2024年第9期42-48,共7页
Pharmacology and Clinics of Chinese Materia Medica
基金
陕西省教育厅专项科研计划项目(编号:21JK0607)
陕西省中医药管理局科研项目(编号:2021-ZZ-JC003)
陕西省自然科学基础研究计划(编号:2022JQ-918)
国家自然科学基金项目(编号:82304504)。
关键词
滋水清肝饮
抑郁症
皮质酮替代饮水抑郁模型
酪氨酸激酶2/细胞外调节蛋白激酶1/2/信号转导和转录激活因子3信号通路
Zishui Qinggan(滋水清肝)Decoction
Depression
Model with CORT Replacing Drinking Water
Januskinase2(JAK2)/Extracellular-regulated kinase 1/2(ERK1/2)/Signal transducer and activator of transcription 3(STAT3)Signaling Pathway
