摘要
目的:基于超高效液相色谱-四级杆-飞行时间质谱(UPLC-Q-TOF/MS)技术探讨参苓白术散对脾虚湿困型溃疡性结肠炎(SDDR-UC)大鼠粪便中内源性标志物的影响,旨在寻找粪便中差异的生物标志物群,从代谢组学的角度阐述参苓白术散改善SDDR-UC的分子机制。方法:将雄性SD大鼠随机分为5组:正常组,SDDR-UC模型组,参苓白术散低、中、高剂量组。采用病症结合法复制脾虚湿困证模型大鼠,再灌胃5%葡聚糖硫酸钠造成SDDR-UC模型。给药阶段,各治疗组灌胃参苓白术散低、中、高剂量(0.472、0.945、1.89 g·kg^(-1)·d^(-1)),正常组、模型组则灌胃灭菌纯净水。实验结束前,收集各组大鼠粪便,应用UPLC-Q-TOF/MS方法测定粪便代谢物的含量,结合多维统计分析筛选组间差异代谢物,并进行Metabo Analyst 5.0代谢通路富集分析。结果:共筛选和鉴定出34个潜在生物标志物,主要影响叶酸生物合成、色氨酸代谢、鞘脂代谢、一个叶酸碳库、花生四烯酸代谢5条代谢通路,其中墨蝶呤、6-羟基褪黑素、1-磷酸鞘氨醇、二氢叶酸和12(S)-白三烯B4是与代谢通路密切相关的关键潜在生物标志物。结论:参苓白术散对SDDR-UC的治疗作用可能与其调控炎性因子的释放、抗脂质过氧化和氧化应激损伤、修复受损屏障、维持结肠上皮细胞黏膜的完整性,进而恢复体内正常代谢活动有关。
Objective: Based on Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS) to investigate the effects of Shenling Baizhu Powder on endogenous markers in feces of spleen deficiency with dampness retention-ulcerative colitis(SDDR-UC) rats,aiming to find different biomarker groups in feces. The molecular mechanism of Shenling Baizhu Powder in improving SDDR-UC was elaborated from the perspective of metabolomics. Methods:Male SD rats were randomly divided into 5 groups: normal group,SDDR-UC model group,low-,medium-and high-dose Shenling Baizhu Powder groups. The SDDR-UC model rats were induced by diet combined with environment intervention and 5%DSS intragastric administration. At the administration stage,the treatment groups were given with low-,medium-,and high-dose(0.472,0.945,1.89 g·kg^(-1)·d^(-1)) of Shenling Baizhu Powder,while normal group and model group were given sterilized pure water. Before the end of the experiment,the fece of rats were collected,and then detected by UPLC-Q-TOF/MS. The differential metabolites associated with this disease were screened by multi-dimensional statistical analysis. Finally,Metabo Analyst 5.0 was used for metabolic pathway enrichment analysis. Results: In this experiment,34 potential biomarkers were screened and identified,which mainly affected 5 metabolic pathways such as Folate biosynthesis,Tryptophan metabolism,Sphingolipid metabolism,One carbon pool by folate and Arachiidonic acid metabolism. Among the above metabolic pathways,Sepiapterin,6-hydroxymelatonin,Sphinganine 1-phosphate,Dihydrofolic acid and 12(S)-leukotriene B4 was key potential biomarkers closely related to their metabolic pathways. Conclusion: Therapeutic effect of Shenlingbaizhu Powder on SDDR-UC rats may be related to its regulation of inflammatory factors release,resistance to lipid peroxidation and oxidative stress injury,repair of damaged barrier,and recovery of normal metabolic activities in the body.
作者
钟薏文
张文彤
陈雅茜
徐霞
王玮玮
涂钰
熊艳玲
徐国良
李冰涛
张启云
姜丽
ZHONG Yi-wen;ZHANG Wen-tong;CHEN Ya-xi;XU Xia;WANG Wei-wei;TU Yu;XIONG Yan-ling;XU Guo-liang;LI Bing-tao;ZHANG Qi-yun;JIANG Li(Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory,Key laboratory of TCM Etiopathogenisis,Key Laboratory of Pharmacology of TCM,Jiangxi University of Chinese Medicine,Nanchang 330004,China;College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210000,China;Affiliated Hospital of Jinggangshan University,Ji’an 343000,China;Department of Clinical Pharmacology,Xiangya Hospital,Central South University,Changsha 410008,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2023年第2期840-847,共8页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
江西中医药大学校级科技创新团队发展计划(No.CXTD22007)
江西省卫生计生委中医药科研课题(No.2021B599)
江西省卫生健康委科技计划课题(No.SKJP_220210795)。
关键词
参苓白术散
脾虚湿困
溃疡性结肠炎
粪便
代谢组学
超高效液相色谱-四级杆-飞行时间质谱
Shenling Baizhu Powder
Spleen deficiency with dampness retention
Ulcerative colitis(UC)
Fecal
Metabonomics
Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)
