基于代谢组学探讨电针对WKY抑郁大鼠的抗抑郁作用  

Antidepressant Effect of Electroacupuncture in WKY Rats of Depression Based on Metabonomics

作　　者：李翔[1] 曾晓铃 顾政平 李珊珊 徐世芬[1] 李蔚 Li Xiang;Zeng Xiaoling;Gu Zhengping;Li Shanshan;Xu Shifen;Li Wei(Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Department of Academic,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China;School of Basic Medical Sciences,Fudan University,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属市中医医院,上海200071 [2]上海交通大学医学院学术部,上海200030 [3]复旦大学基础医学院,上海200231

出　　处：《世界科学技术-中医药现代化》2022年第6期2186-2194,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(81973943):针刺通过调节拟杆菌/TpH介导宿主5-HT合成干预抑郁大鼠的肠-脑双向调节机制,负责人:徐世芬;上海市卫健委医学领军人才项目(2019LJ06):基于p11介导mGluR5膜定位探究电针对抑郁小鼠行为的作用机制,负责人:徐世芬。

摘　　要：目的采用液质联用非靶向代谢组学技术探究电针抗抑郁的作用机制方法将24只雄性WKY大鼠随机分为模型组、电针组、假针组,每组8只。Wistar雄性大鼠8只设为对照组。电针组于“百会”“足三里”进行电针治疗,每次20 min,1周5次,连续治疗3周。假针组取穴同电针组,毫针不刺破皮肤,毫针与电针仪导线相连,但无电流通过。最后通过旷场实验、强迫游泳和新奇抑制摄食实验评价行为学改变;对照组、模型组和电针组大鼠粪便采用高效液相-色谱质谱系统分析代谢物及组成的变化,探究抑郁症核心生物标记物的代谢途径差异,以评价电针的抗抑郁作用机制。结果与对照组相比,模型组在旷场试验中的直立次数减少(P<0.001),中央运动距离减少(P<0.05);强迫游泳的不动时间延长(P<0.001);新奇抑制摄食潜伏摄食时间增加(P<0.001)。与假针组相比,电针组在旷场试验中的直立次数增加(P<0.001),中央运动距离增加(P<0.05);强迫游泳的不动时间减少(P<0.001);新奇抑制摄食潜在摄食时间减少(P<0.001)。通过模式识别分析发现,WKY大鼠代谢产物发生显著差异,电针后的代谢产物也出现明显差异。对显著性差异代谢产物分析发现,甜菜苷在模型组中升高,在电针组中降低;环己基氨基磺酸酯、10-氢过氧-H4-神经前列腺素、15(S)-羟基二十碳三烯酸、地奥司明在模型组中降低,在电针组中升高。KEGG通路结果发现显著差异代谢产物主要参与了脂质代谢、氨基酸代谢、生物素降解与代谢等代谢途径。结论电针能改变抑郁大鼠的抑郁样行为,可能是通过调节脂质代谢、氨基酸代谢、生物素降解与代谢等代谢途径发挥抗抑郁的治疗作用。Objective To explore the anti-depression mechanism of electroacupuncture by LC-MS non-targeted metabonomics.Methods Twenty-four male WKY rats were randomly divided into model group,electroacupuncture group and sham-acupuncture group,with 8 rats in each group.Eight male Wistar rats were set as normal group.The electroacupuncture group was treated with electroacupuncture at Baihui(DU20)and Zusanli(ST36)for 20 min each time,5 times a week for 3 weeks.The acupoints in the sham acupuncture group were the same as those in the electroacupuncture group.The filiform needles did not pierce the skin,and the filiform needles were connected with the wires of the electroacupuncture instrument,but no current passed through.Finally,the behavioral changes were evaluated by open field test,forced swimming test and novelty suppressed feeding.In order to evaluate the antidepression mechanism of electroacupuncture,the changes of metabolites and compositions in feces of rats in normal group,model group and electroacupuncture group were analyzed by HPLC-MS system,and the differences of metabolic pathways of core biomarkers of depression were explored.Results Compared with the control group,the rearing times in the open field test of rats in the model group were decreased(P<0.001),and the central distance was decreased(P<0.05).The immobility time of forced swimming test was prolonged(P<0.001);Latency for novelty suppressed feeding was increased(P<0.001).Compared with the sham acupuncture group,the rearing times in the open field test were increased in the EA group(P<0.001),and the central distance was increased(P<0.05).The immobility time of forced swimming test was decreased(P<0.001);Latency for novelty suppressed feeding was decreased(P<0.001).Through pattern recognition analysis,the metabolism of WKY rats was significantly different,and the metabolites after electroacupuncture were also significantly different.The analysis of significantly different metabolites showed that Betavulgaroside VII increased in the model group and decrease

关 键 词：抑郁症 代谢组学 电针 代谢通路 WKY抑郁大鼠 

分 类 号：R245.9[医药卫生—针灸推拿学]