消胀贴膏敷脐治疗肝硬化腹水的临床代谢组学研究

为分析消胀贴膏敷脐改善肝硬化腹水的生物标志物与作用机制,为其临床应用提供科学依据,将2017年11月至2018年6月于上海中医药大学附属曙光医院确诊为肝硬化腹水伴有胃肠动力障碍的住院患者分为安慰剂组(4例)和消胀贴膏组(5例),并纳入10例健康志愿者作为对照。试验获得上海中医药大学附属曙光医院伦理委员会批准(批件号:2017-528-11-01)。消胀贴膏组患者给予消胀贴膏脐部贴敷,安慰剂组给予生药含量低于5%的凝胶贴膏,每日1贴,连续3日。采用非靶向代谢组学研究方法,结合UPLC-Q/Orbitrap-MS/MS分析技术,对给药前后患者尿液中内源性代谢轮廓的变化进行分析。通过系统分析比较肝硬化腹水患者与健康志愿者的尿液代谢轮廓,最终指认了31个生物标志物,其中14个生物标志物受消胀贴膏干预有显著回调(P<0.05),通路富集分析发现苯丙氨酸与色氨酸代谢通路是消胀贴膏发挥药效的关键通路。消胀贴膏改善肝硬化腹水的作用机制可能与调节机体氨基酸及其代谢产物的水平相关。

Clinical metabolomics research on Xiaozhang Tie with the umbilical compress therapy for cirrhotic ascites

We used metabolomics technology to identify and understand the biomarkers and therapeutic mecha‐nisms of umbilical compress therapy based on Xiaozhang Tie(XT)to provide scientific evidence for its clinical application.A total of 10 patients with cirrhotic ascites and gastrointestinal motility disorders who were hospitalized in the Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2017 to June 2018 were divided into a placebo group(4 cases)or an XT group(5 cases),and 10 healthy volunteers were included as controls.This clinical trial was approved according to the Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine(2017-528-11-01).The patients in the XT group were given umbilical compress therapy with Xiaozhang Tie,and patients in the placebo group were administered a plaster patch in which the drug content was less than 5%,receiving one patch per day for three consecutive days.Non-targeted metabolomics technology and UPLC-Q/Orbitrap-MS/MS analysis technology were utilized to investigate the fluctuations in endogenous metabolic profiles in the patient's urine prior to and after administration of XT.By analyzing and comparing the urine metabolic profiles of patients with cirrhotic ascites to those of healthy volunteers,a total of 31 biomarkers were identified,14 of which were significantly decreased by the inter‐vention with Xiaozhang Tie(P<0.05).Pathway enrichment analysis revealed that phenylalanine metabolism and tryptophan metabolism are key pathways affected by XT treatment.The results suggest that XT can alleviate cirrhotic ascites by modulating abnormalities in amino acid metabolism.