辛弗林对CUMS大鼠抑郁样行为和血清代谢组学的影响  

Effects of Synephrine on Depression-Like Behavior and Serum Metabonomics in CUMS Rats

作　　者：谢杞 王云 徐秋月 严函 肖哲 黄熙[1] 任平[1] XIE Qi;WANG Yun;XU Qiu-yue;YAN Han;Xiao Zhe;HUANG Xi;REN Ping(Institute of TCM Related Comorbid Depression,Nanjing University of Chinese Medicine,Nanjing,210023,China;School of Medicine,Xiamen University,Xiamen,361005,China;School of Medicine and Life Sciences,Nanjing University of Chinese Medicine,Nanjing,210023,China)

机构地区：[1]南京中医药大学共病郁证研究所,江苏南京210023 [2]厦门大学医学院,福建厦门361005 [3]南京中医药大学医学与生命科学学院,江苏南京210023

出　　处：《南京中医药大学学报》2019年第5期590-595,共6页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金(81573797,81072967);江苏高校优势学科建设工程资助项目(中西医结合)

摘　　要：目的通过观察分析大鼠慢性应激引起的行为学和血清代谢组变化以及辛弗林抗抑郁的有效治疗,发现潜在的抗抑郁新药先导化合物和生物标志物。方法将24只大鼠分为正常组、模型组和辛弗林组。模型组为6周慢性温和不可预知应激(CUMS)模型大鼠,用体质量变化、糖水偏好、开场实验作为抑郁评估指标,后2周辛弗林(Syn 20 mg/kg)干预治疗后采集大鼠血清进行气相色谱质谱联用(GC-MS/MS)测定,研究CUMS大鼠血清内源性代谢物变化,以及辛弗林的干预作用,寻找其抗抑郁潜在的先导化合物和生物标志物,并找到相关靶向代谢通路。结果辛弗林干预后,在增加CUMS大鼠体质量、提高糖水偏好率、增加开场运动总距离和理毛次数的同时,还能逆转CUMS大鼠血清中磷酸乙醇胺、苯甲酸、胆固醇、谷氨酸等14种代谢物的变化使其趋于正常组,并发现谷氨酰胺和谷氨酸的代谢、缬氨酸和异亮氨酸的生物合成等9条主要牵涉辛弗林的靶向代谢通路。结论辛弗林可能通过调节谷氨酰胺和谷氨酸的代谢、缬氨酸和异亮氨酸的生物合成等生物学途径发挥对CUMS大鼠抑郁样行为的调正作用。OBJECTIVE To identify potential anti depressant lead compounds and biomarkers,through observing the behavioral and serum metabolome changes induced by chronic stress in rats.METHODS Twenty-four rats were randomly divided into three groups including normal,model and treatment groups.Six-week of chronic unpredictable mild stress(CUMS)of rats were chosen as chronic depressed model.Weight change,sucrose water preference and opening test were used as indicators of depression assessment.Synephrine(Syn 20 mg/kg)was gavaged once a day in late two weeks.After two weeks of intervention,the serum of rats was collected,and GC MS/MS were used to detect the changes of endogenous metabolites in rat serum and the drug therapy,to discover potent anti depressant lead compound,biomarker and relative pathway.RESULTS Synephrine alleviated depression-like behavior and changed 14 metabolites including ethanolamine phosphate,benzoic acid,cholesterol and glutamic acid in CUMS rat serum.Nine targeted metabolic pathways involving synephrine,such as glutamine and glutamate metabolism,valine and isoleucine biosynthesis,were discovered.CONCLUSION Synephrine may be against depression like behavior mainly via regulating mechanism and biosynthesis from glutamate,valine and isoleucine.

关 键 词：辛弗林 抑郁症 慢性温和不可预知应激 代谢组学 气相色谱质谱联用 

分 类 号：R917[医药卫生—药物分析学]