醋甘遂对Walker-256腹水模型大鼠的粪便代谢组学研究  

Effect of Kansui Radix stir-fried with vinegar on fecal metabolomics in Walker-256 rats with ascites

作　　者：周世康 姜东京 张毅[1] 张丽[1] ZHOU Shi-kang;JIANG Dong-jing;ZHANG Yi;ZHANG Li(Jiangsu Provincial Collaborative Innovation Center for Industrialization Process of Traditional Chinese Medicine Resources/National-Local Joint Engineering Research Center for Traditional Chinese Medicine Resources Industrialization,Prescriptions and Innovative Drugs,Nanjing University of Chinese Medicine,Nanjing 210023,China;School of Pharmacy,Suzhou Vocational Health College,Suzhou 215000,China)

机构地区：[1]南京中医药大学,江苏省中药资源产业化过程协同创新中心,中药资源产业化与方剂与创新药物国家地方联合工程研究中心,江苏南京210023 [2]苏州卫生职业技术学院药学院,江苏苏州215000

出　　处：《中国中药杂志》2022年第6期1558-1566,共9页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81673599);江苏省333工程人才项目(BRA2020071);江苏省自然科学基金项目(BK20201232)。

摘　　要：基于代谢组学技术,研究醋甘遂对Walker-256细胞癌性腹水模型大鼠的粪便内源性代谢物变化,寻找与醋甘遂治疗癌性腹水相关的粪便潜在生物标志物,探讨醋甘遂粉末对腹水模型大鼠泻水逐饮的作用机制。采用快速液相色谱串联四极杆飞行时间质谱(UFLC-Q-TOF-MS)技术,对各组大鼠粪便样本进行测定,应用主成分分析(PCA)、偏最小二乘-判别分析(PLS-DA)等多种方法进行模式识别,结合t检验和变量投影重要性(VIP)筛选出与癌性腹水相关的潜在生物标志物,并基于MetaboAnalyst进行通路分析,最后联合肠道菌群测序结果相关分析,阐释醋甘遂的泻水作用机制。结果显示,生/醋甘遂粉末均可使模型大鼠体内异常代谢有所恢复,醋甘遂的调节作用弱于生甘遂。共筛选鉴定出11种癌性腹水潜在生物标志物、5条代谢通路和4种肠道菌。醋甘遂的泻水逐饮作用与调节苯丙氨酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成,色氨酸代谢,甘油磷脂代谢,糖基磷脂酰肌醇生物合成等代谢通路有关。该研究为深入理解与醋甘遂泻水逐饮效应相关的肠道菌群-宿主相互作用提供科学依据,并为醋甘遂临床合理应用提供参考。Utilizing metabolomics technology,this study explored the change of fecal endogenous metabolites in Walker-256 rats with malignant ascites after the administration with Kansui Radix(KR)stir-fried with vinegar(VKR),sought the potential biomarkers in feces which were related to the treatment of malignant ascites by VKR and revealed the biological mechanism of water-expelling effect of VKR.Ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometry(UFLC-Q-TOF-MS)was employed to detect the feces of rats in all groups.Principle component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)were conducted to achieve pattern recognition.Combining t-test and variable importance in the projection(VIP)enabled the screening of potential biomarkers for the malignant ascites.Metabolic pathway analysis was accomplished with MetaboAnalyst.Correlation analysis was finally conducted integrating the sequencing data of gut microbiota to elucidate the mechanism underlying the water-expelling effect of VKR.The results showed that both KR and VKR could restore the abnormal metabolism of model rats to some extent,with VKR being inferior to KR in the regulation.Eleven potential biomarkers were identified to be correlated with the malignant ascites and five metabolic pathways were then enriched.Four kinds of gut microbiota were significantly related to the potential biomarkers.The water-expelling effect of VKR may be associated with the regulation of phenylalanine metabolism,biosynthesis of phenylalanine,tyrosine and tryptophan,tryptophan metabolism,glycerophospholipid metabolism,and glycosylphosphatidylinositol(GPI)-anchor biosynthesis.This study can provide a scientific basis for comprehensive understandings of the interaction between gut microbiota and host which has relation to the water-expelling effect of VKR and guide the reasonable clinical application of VKR.

关 键 词：醋甘遂 癌性腹水 粪便代谢组学 代谢通路分析 

分 类 号：R285.5[医药卫生—中药学]