柴胡疏肝散对抑郁模型大鼠粪便代谢物组和肠道菌群的调控作用  

The regulatory effects of Chaihu-Shu-Gan-San on fecal metabolome and gut microbiota in depression model rats

作　　者：于猛[1] 贾红梅[1] 张宏武[1] 张涛[1] 尚海[1] 马丽焱[1] 邹忠梅[1] YU Meng;JIA Hong-mei;ZHANG Hong-wu;ZHANG Tao;SHANG Hai;MA Li-yan;ZOU Zhong-mei(Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院&北京协和医学院药用植物研究所,北京100193

出　　处：《国际药学研究杂志》2020年第3期229-235,共7页Journal of International Pharmaceutical Research

基　　金：国家“重大新药创制”科技重大专项资助项目(2019ZX09735002);国家自然科学基金资助项目(81673584)。

摘　　要：目的研究抗抑郁经典方剂柴胡疏肝散(CSGS)对抑郁模型大鼠粪便代谢物组和肠道菌群的调控作用。方法采用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)代谢组学分析技术,研究CSGS对烟酸、次黄嘌呤等16个抑郁相关粪便差异代谢物的调控作用;采用16S rRNA基因测序分析技术,研究CSGS从3个门水平(厚壁菌门、拟杆菌门和变形菌门)及11个属水平(分节丝状菌属、颤杆菌属、…)对肠道细菌丰度变化的调控作用。结果与正常大鼠相比,抑郁模型大鼠体质量增长缓慢(P<0.01)、旷场实验自主活动次数减少(P<0.01)、糖水偏嗜度显著降低(P<0.01),给药CSGS和阳性药后,均能明显改善抑郁大鼠体质量增长缓慢(P<0.01),且能显著提高抑郁大鼠自主活动次数减少(P<0.01)和糖水偏嗜度下降的现象(P<0.01)。此外,CSGS可显著回调厚壁菌门肠道细菌的门水平丰度降低,而阳性药氟西汀不能调节它的降低趋势。同时,CSGS能显著抑制拟杆菌门和变形菌门肠道细菌的门水平细菌丰度异常升高。另外,给CSGS后,可对肠道细菌中丰度较大的3个属水平细菌包括降低的乳杆菌属(Lactobacillus)和纺锤状细菌属(Christensenella)及升高的颤杆菌属进行正向调控,趋于正常水平。结论CSGS对抑郁导致的粪便代谢物组改变具有正向调控作用,其调控作用机制可能是部分通过调控肠道菌群,从而改变肠道菌群相关的粪便代谢产物而发挥抗抑郁作用。Objective To investigate the regulatory effects of Chaihu-Shu-Gan-San(CSGS)on fecal metabolome and gut microbiota in depression model rats.Methods The UPLC-Q-TOF/MS-based metabolomics approach was used to investigate the regulatory effect of CSGS on the depression-related 16 fecal metabolites,such as nicotinic acid and hupoxianthine.Meanwhile,the 16 S rRNA analysis was performed to investigate the regulator effects of CSGS on the microbiota in 3 phylum levels(Firmicutes,Bacteroidetes,and Proteobacteria)and 11 genus levels(Candidatus arthromitus,Oscillibacter,etc.).Results The change rate of body weight(P<0.01),the number of rearing and crossing(P<0.01)and the sucrose preference(P<0.01)in the depression rat group presented a significant decrease compared with control group.While rats in the CSGS group and fluoxetine group showed a significant increase in the body weight(P<0.01),the number of rearing and crossing(P<0.01),and the sucrose preference(P<0.01)compared with model group.In addition,the decreased level of Firmicutes was positively regulated by CSGS but not fluoxetine,and the increased Bacteroidetes and Proteobacteria levels were also down-regulated by CSGS.Meanwhile,the abnormal levels of 3 genera of the gut microbiota with high abundance of Oscillibacter and low abundance of Lactobacillus and Christensenella,were all regulated to a nearly normal level by CSGS.Conclusion CSGS could reverse changes of fecal metabolome in depression model rats by positive regulation,and CSGS likely exerts its antidepressant effect via regulating the gut microbiota,at least partially,to alter the related metabolites.

关 键 词：CSGS 抑郁症 粪便代谢物组 肠道菌群 

分 类 号：R285[医药卫生—中药学]