胆腑郁热型慢性鼻-鼻窦炎患者尿液代谢组学研究

Urine metabolomics in patients with chronic rhinosinusitis of type of heat stagnation in gallbladder

目的寻找胆腑郁热型慢性鼻-鼻窦炎(CRS)患者尿液中内源性小分子代谢标志物,为明确其发病机制及治疗提供一定依据。方法选择2019年4月—2021年10月在黑龙江中医药大学附属第一医院耳鼻喉科门诊就诊的20例胆腑郁热型CRS患者作为CRS组,选择同期就诊的20例鼻中隔偏曲患者作为对照组,采用液相色谱-质谱(UPLC-MS/MS)方法分析2组患者尿液代谢物的差异,并对潜在代谢标志物进行鉴定和分析。结果与对照组比较,CRS组患者尿液中N-乙酰组胺、咪唑丙酸、去甲肾上腺素、香草扁桃酸、N-乙酰鸟氨酸、L-脯氨酸、2-氨基苯甲酸、氧戊二酸、甲基琥珀酸、4-吡哆酸、2-哌啶酮含量均明显上升(P均<0.05),核黄素、四氢新蝶呤含量均明显下降(P均<0.05)。差异代谢物主要涉及精氨酸合成、酪氨酸代谢、核黄素代谢、D-谷氨酰胺和D-谷氨酸代谢、维生素B 6代谢、丁酸代谢、柠檬酸循环(TCA循环)、丙氨酸、天冬氨酸和谷氨酸的代谢、精氨酸和脯氨酸代谢等代谢通路。结论胆腑郁热型CRS患者与鼻中隔偏曲患者的尿液代谢图谱存在差异,进一步揭示了其发病机制,为CRS中医证候研究提供了一定物质基础。

Objective It is to search for endogenous small molecule metabolic markers in the urine of patients with chronic rhinosinusitis(CRS)of type of heat stagnation in gallbladder,to provide some evidence for clarifying its pathogenesis and treatment.Methods Twenty patients with CRS of type of heat stagnation in gallbladder treated in the outpatient clinic of the Department of Otorhinolaryngology of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from April 2019 to October 2021 were selected as the CRS group,and 20 patients with deviated nasal septum treated during the same time period were selected as the control group.The differences in urinary metabolomics of patients in the 2 groups was analyzed by liquid chromatography-mass spectrometry(UPLC-MS/MS)method,and the potential metabolic markers were identified and analyzed.Results Compared with the control group,the urinary contents of N-acetylhistamine,imidazolepropionic acid,norepinephrine,vanillylmandelic acid,N-acetylornithine,L-proline,2-aminobenzoic acid,oxypentanedioic acid,methylsuccinic acid,4-pyridoxic acid,and 2-piperidinone in patients of the CRS group were significantly increased(all P<0.05),and the contents of riboflavin and tetrahydronephosphingosine were significantly decreased(all P<0.05).The differential metabolites mainly involved metabolic pathways such as arginine synthesis,tyrosine metabolism,riboflavin metabolism,D-glutamine and D-glutamate metabolism,vitamin B 6 metabolism,butyric acid metabolism,citric acid cycle(TCA cycle),the metabolism of alanine,aspartic acid,and glutamic acid,and arginine and proline metabolism.Conclusion There was differences in urinary metabolic profiles between patients with CRS of type of heat stagnation in gallbladder and patients with deviated nasal septum,which further reveal their pathogenesis and provide a certain material basis for the study of Chinese medical syndrome of CRS.