桑菊解郁方对行为绝望模型和嗅球切除模型小鼠的抗抑郁作用及机制研究  

Study on antidepressant effect and mechanism of Sangju Jieyu Formula on behavioral despair mouse model and on olfactory bulbectomized mouse model

作　　者：沈鑫明 张杨 薛瑞 罗亚 李硕 李劲草 苏瑞斌 张有志 SHEN Xinming;ZHANG Yang;XUE Rui;LUO Ya;LI Shuo;LI Jincao;SU Ruibin;ZHANG Youzhi(Nanjing University of Chinese Medicine,Nanjing 210046,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;School of Medicine,Anhui University of Science and Technology,Huainan 232001,China)

机构地区：[1]南京中医药大学,南京210046 [2]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室 [3]安徽理工大学医学院

出　　处：《北京中医药大学学报》2023年第10期1382-1390,共9页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81274117)。

摘　　要：目的探讨药食同源中药复方桑菊解郁方的抗抑郁作用及潜在作用机制。方法(1)行为绝望模型实验。通过悬尾、强迫游泳和自发活动复制模型。将小鼠分为对照组,度洛西汀组(悬尾实验10 mg/kg,强迫游泳及自发活动实验各20 mg/kg),桑菊解郁方低、中、高剂量组(267.4、534.8、1069.5 mg/kg),评价桑菊解郁方单次灌胃给药的抗抑郁作用。(2)嗅球切除模型实验。将小鼠分为假手术组,模型组,度洛西汀组(10 mg/kg),桑菊解郁方中、高剂量组(534.8、1069.5 mg/kg),灌胃给药15 d,采用毛发评估实验、自发活动实验和悬尾实验评价桑菊解郁方的抗抑郁作用,并采用ELISA检测各组小鼠海马组织丙二醛(MDA)、超氧化物歧化酶(SOD)含量,采用蛋白质印迹法检测小鼠海马胱天蛋白酶3(CASP3)和突触后致密蛋白95(PSD-95)蛋白表达水平。结果(1)在行为绝望模型实验中,单次灌胃高剂量桑菊解郁方及度洛西汀可缩短小鼠悬尾不动时间(P<0.05),单次灌胃各剂量桑菊解郁方及度洛西汀可缩短小鼠游泳不动时间(P<0.05),且在有效剂量范围内对中枢神经系统无兴奋和抑制作用。(2)在小鼠嗅球切除模型实验中,与假手术组比较,模型组小鼠自发活动增多、悬尾不动时间增长、毛发评分下降(均P<0.05);小鼠海马组织中MDA含量增加,SOD含量下降(均P<0.05);CASP3蛋白表达增加,PSD-95蛋白表达减少(均P<0.05)。与模型组比较,高剂量桑菊解郁方组和度洛西汀组上述改变均被逆转(均P<0.05)。结论桑菊解郁方具有抗抑郁作用,其作用机制可能与抗氧化应激、抗海马细胞凋亡和增强突触可塑性有关。Objective We aimed to evaluate the antidepressant effect of the Chinese medical compound formula—Sangju Jieyu Formula(SJJY)and the underlying mechanism.Methods(1)Behavioral despair model experiment.The model was established through tail suspension,forced swimming and spontaneous locomotro activity.Mice were divided into the control group,the duloxetine group(10 mg/kg in the tail suspension test[TST],20 mg/kg in the forced swimming test[FST]and the spontaneous locomotor activity test[SLAT]),and the SJJY groups(267.4,534.8,and 1069.5 mg/kg).The antidepressant activity of a single intragastric administration of SJJY was evaluated by conducting the TST,FST,and SLAT.(2)Olfactory bulbectomized(OB)model experiment.Mice were divided into the sham-operation group,the model group,the duloxetine(10 mg/kg)group,and the SJJY groups(534.8 and 1069.5 mg/kg).Duloxetine and SJJY were administered intragastrically for 15 days.The coat state test(CST),SLAT,and TST were conducted to evaluate the antidepressant activity of SJJY when administered multiple times,and ELISA was used to detect the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in hippocampal tissues.Western blotting was conducted to determine the hippocampal expression levels of caspase-3(CASP3)and post synaptic density 95(PSD-95).Results(1)In the behavioral despair experiment,a single dose of SJJY(1069.5 mg/kg)or duloxetine(10 mg/kg)significantly shortened the suspension immobility time(P<0.01),and a single dose of SJJY(267.4,534.8,or 1069.5 mg/kg)or duloxetine(20 mg/kg)significantly shortened the swimming immobility time(P<0.05).These effective doses had no excitatory or inhibitory effect on the central nervous system.(2)In the OB model experiment,compared with the model group,administration of SJJY(1069.5 mg/kg)reversed OB-induced elevated spontaneous activity,increased the TST immobility time,decreased the coat state score(all P<0.05),upregulated hippocampal MDA levels,downregulated SOD levels(both P<0.05),upregulated hippocampal CASP3 protein levels,and

关 键 词：桑菊解郁方 药食同源 抗抑郁 行为绝望模型 嗅球切除模型 氧化应激 细胞凋亡 小鼠 

分 类 号：R285.5[医药卫生—中药学]