中国药房2024，Vol.35Issue(9)：1064-1069,6.DOI:10.6039/j.issn.1001-0408.2024.09.07
甲巯咪唑对甲状腺功能亢进症大鼠尿液代谢组学的影响研究
Effects of methimazole on urinary metabolomics in hyperthyroidism rats
摘要
Abstract
OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats,and to preliminarily investigate its possible mechanism.METHODS Thirty SD rats were randomly divided into control group,model group and methimazole group,with 10 rats in each group.Except for the control group,the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days;at the same time,methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day.The basic condition of the rats was observed,and the body weight and anal temperature were measured.After the last medication,the serum levels of triiodothyronine(T3),tetraiodothyronine(T4),free triiodothyronine(FT3),free tetraiodothyronine(FT4),and thyroid stimulating hormone(TSH)were determined;24-hour urine was collected on the 15th day after administration.UPLC-TOF-MS was used to analyze the urine metabolomics of rats.Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites,and potential metabolic pathways were analyzed by using HMDB and KEGG.RESULTS Compared with the control group,the rectal temperature,serum levels of T3,T4,FT3 and FT4,the expressions of differential metabolites sebacic acid,cholic acid 3-O-glucuronic acid and N6,N6,N6-trimethyl-L-lysine in urine were significantly up-regulated,while body weight,serum level of TSH,the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated(P＜0.01).Compared with model group,above indexes of rats were reversed significantly in methimazole group(P＜0.01 or P＜0.05).Above five differential metabolites were mainly involved in four signaling pathways:pentose and glucuronate interaction,lysine degradation,cysteine and methionine metabolism,and pyrimidine metabolism.CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction,lysine degradation,cysteine and methionine metabolism,and pyrimidine metabolism.关键词
甲巯咪唑/甲状腺功能亢进症/尿液代谢组学/差异代谢物/超高效液相色谱-飞行时间质谱Key words
methimazole/hyperthyroidism/urine metabolomics/differential metabolites/UPLC-TOF-MS分类
医药卫生引用本文复制引用
卢旭,李玲,叶涛,彭佑锋,何佳馨,张宁..甲巯咪唑对甲状腺功能亢进症大鼠尿液代谢组学的影响研究[J].中国药房,2024,35(9):1064-1069,6.基金项目
国家自然科学基金项目(No.82060830) （No.82060830）
贵州省科技计划项目(自然科学类)(No.黔科合基础-ZK[2024]重点073) （自然科学类）
贵州省卫生健康委科学技术基金项目(No.gzwkj2021-457) （No.gzwkj2021-457）
贵州中医药大学大学生创新创业训练计划项目(No.贵中医大创合字[2021]74号) （No.贵中医大创合字[2021]74号）
