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.
Zhongguo Zhong Yao Za Zhi. 2022 Mar;47(6):1558-1566. doi: 10.19540/j.cnki.cjcmm.20210412.305.
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.
本研究利用代谢组学技术,探讨醋炙甘遂(VKR)对Walker-256恶性腹水大鼠粪便内源性代谢产物的影响,寻找与VKR治疗恶性腹水相关的粪便潜在生物标志物,揭示VKR逐水作用的生物学机制。采用超快速液相色谱-四极杆-飞行时间质谱(UFLC-Q-TOF-MS)检测各组大鼠粪便。进行主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)以实现模式识别。结合t检验和投影变量重要性(VIP)筛选恶性腹水潜在生物标志物。用MetaboAnalyst完成代谢通路分析。最后结合肠道微生物群测序数据进行相关性分析,以阐明VKR逐水作用的潜在机制。结果表明,甘遂(KR)和VKR均能在一定程度上恢复模型大鼠的代谢异常,VKR在调节作用上略逊于KR。鉴定出11种与恶性腹水相关的潜在生物标志物,富集了5条代谢通路。4种肠道微生物群与潜在生物标志物显著相关。VKR的逐水作用可能与苯丙氨酸代谢、苯丙氨酸、酪氨酸和色氨酸的生物合成、色氨酸代谢、甘油磷脂代谢以及糖基磷脂酰肌醇(GPI)-锚生物合成的调节有关。本研究可为全面了解与VKR逐水作用相关的肠道微生物群与宿主之间的相互作用提供科学依据,并指导VKR的合理临床应用。