基于嗅球摘除模型大鼠柴当薄组方挥发油抗抑郁作用及Nrf2/HO-1机制  

Study on antidepressant effects of Nrf2/HO-1 of volatile oil from Chai Dang Bo drug-group on OB model rats and its mechanism

作　　者：胡靖文 谢志强 曾九僧 秦甜甜 谢红潇 刘蓉[1] 曾南[1,2] HU Jing-wen;XIE Zhi-qiang;ZENG Jiu-seng;QIN Tian-tian;XIE Hong-xiao;LIU Rong;ZENG Nan(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]西南特色中药资源国家重点实验室,四川成都611137

出　　处：《中国药理学通报》2023年第8期1507-1514,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81503277,82074094);四川省科技厅应用基础研究项目(No 2020YJ0388)。

摘　　要：目的采用嗅球摘除(olfactory bulbectomy,OB)抑郁样模型大鼠探究逍遥散精简方柴当薄(Chai Hu,Dang Gui,Bo He,CDB)组方挥发油部位的抗抑郁作用及其干预Nrf2/HO-1通路的作用机制。方法GC-MS分析CDB挥发油部位主要成分。大鼠实施OB造模后14 d,分为模型组、盐酸氟西汀(10 mg·kg^(-1))、CDB水煎液(15.33 g生药·kg^(-1))、CDB挥发油部位高、低剂量(46、23 mg·kg^(-1))、假手术6个组。大鼠连续灌胃28 d,d 14、28进行糖水偏好与旷场试验,d 28进行飞溅试验。检测大鼠血清及皮质中超氧化物歧化酶(SOD)、还原性谷胱甘肽(GSH)水平,血清肿瘤坏死因子(TNF-α)水平及皮质中丙二醛(MDA)含量。检测海马部位Nrf2、HO-1蛋白表达量及HO-1、GPX3、NQO1 mRNA表达水平。结果CDB挥发油中含量较丰富的成分主要有藁本内酯、薄荷脑、香芹酮、丁烯基苯酞等。CDB挥发油可使模型大鼠糖水偏好率增加、水平活动减少、梳洗时间延长,血清和皮质中SOD、GSH水平提高,皮质MDA含量及血清TNF-α水平下降。并使模型大鼠海马Nrf2、HO-1蛋白及HO-1、GPX3、NQO1 mRNA表达水平增加。结论CDB组方挥发油部位能改善OB模型大鼠的抑郁样行为,作用发挥与激活Nrf2/HO-1通路呈现的抗氧化作用有关。Aim To confirm the antidepressant effect of the volatile oil part of the disassembled prescription drugs(Chai Hu,Dang Gui and Bo He,referred to as CDB)from Xiaoyao Powder and investigate its mechanism via Nrf2/HO-1 signaling pathway on OB model rats.Methods GC-MS analysis of the main components of volatile oil part of CDB was performed.The rats were randomly divided into sham operation group,model group,fluoxetine hydrochloride group(FLX,10 mg·kg^(-1)),CDB decoction group(15.33 g·kg^(-1) in raw dose),high and low dose CDB volatile oil group(46 mg·kg^(-1) and 23 mg·kg^(-1) in raw drug quantity),and the rest period was two weeks after surgery.All rats were gavaged continuously for 28 days,and sugar water preference test and open field test were performed on days 14 and 28.Sugar water preference test,open field test and splash test were performed on day 28.After 28 days of administration,rats were anesthetized and the blood was collected from the abdominal aorta,and serum was isolated to determine the levels of superoxide dismutase(SOD)and reduced glutathione(GSH)by biochemical kit.The level of tumor necrosis factor(TNF-α)from serum was detected by enzyme-linked immunosorbent assay(ELISA).The cortex and hippocampus of rats were dissected on an ice table immediately after blood collection,and the levels of malondialdehyde(MDA),SOD and GSH in the cortex were measured.The protein expression of Nrf2,HO-1 in hippocampus were detected by Western blot.The mRNA expressions of HO-1,GPX3 and NQO1 were detected by RT-PCR.Results GC-MS results showed that the components rich in CDB volatile oil were mainly ligustilide,menthol,carvone,butenylphthalide,eucalyptol,etc.Compared with the sham operated group,the OB model rats showed behavioral abnormalities with decreased sucrose preference,increased horizontal activity and decreased grooming time,decreased levels of SOD and GSH in cortex and serum,increased level of MDA in cortex,increased level of TNF-α in serum,and hippocampal Nrf2/HO-1 pathway was inhibited.Compared with th

关 键 词：柴当薄组方 挥发油 嗅球摘除模型 SOD GSH Nrf2/HO-1 

分 类 号：R-332[医药卫生] R289.5R322.81R749.41R749.42