葛根芩连汤含药血清调节缺氧诱导L02细胞糖代谢的影响及代谢机制  

The analysis of effect of serum containing Gegen Qinlian Decoction on regulating hypoxia-induced glucose metabolism in L02 Cells and related metabolic mechanisms

作　　者：游燕[1] 崔红静 彭程程 姜丽 张启云 李冰涛 徐国良 YOU Yan;CUI Hongjing;PENG Chengcheng;JIANG Li;ZHANG Qiyun;LI Bingtao;XU Guoliang(Department of Pharmacy,the Fourth Affiliated Hospital of Nanchang University,Nanchang 330003,Jiangxi,China;不详)

机构地区：[1]南昌大学第四附属医院药学部,江西南昌330003 [2]江西省中医病因生物学重点实验室,江西南昌330004 [3]江西省中药药理重点实验室,江西南昌330004

出　　处：《实用医学杂志》2025年第7期936-943,共8页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82060826)。

摘　　要：目的探讨葛根芩连汤(GQD)含药血清对缺氧诱导L02细胞糖代谢的影响及代谢机制。方法缺氧条件下评估5个时点(6、12、18、24、48 h)对L02细胞葡萄糖消耗及细胞活力的影响,筛选最适缺氧时间;将正常肝细胞作为正常对照组、缺氧诱导L02细胞糖耗量降低分为缺氧组、二甲双胍2 mmol/L组、25 g/kg GQD含药血清5%、10%、15%组,以葡萄糖消耗量为药效指标,采用高分辨液相色谱串联四极杆飞行时间质谱(UPLC-Q-TOF-MS)收集各组细胞内的代谢产物信号,以Progenesis QI软件分析数据,通过HMDB等在线数据库,鉴定潜在生物标记物,进一步借助Metabo Analyst 5.0网站分析潜在生物标记物的代谢途径。结果缺氧18 h被确定为缺氧诱导L02细胞模型复制的最佳时间,在此条件下,GQD5%、10%浓度的含药血清能显著提高缺氧L02细胞的葡萄糖消耗量;鉴定出14种缺氧诱导的L02细胞生物标志物,其中13种显著升高,1种显著降低,而GQD含药血清可使其中3种显著回调。结论GQD含药血清可能通过调控甘油磷脂代谢、糖基磷脂酰肌醇生物合成及鞘脂代谢通路,改善缺氧诱导的L02细胞糖代谢异常,并提升葡萄糖消耗。Objective The study aimedto investigate the effects and metabolic mechanisms of Gegen Qinlian Decoction(GQD)containing serum on hypoxia⁃induced glucose metabolism in L02 cells.Methods The effects of five hypoxia durations(6,12,18,24,and 48 hours)on glucose consumption and cell viability of L02 cells were examined under hypoxic conditions to determine the optimal hypoxia time.Normal hepatocytes served as the normal control group.L02 cells with hypoxia⁃induced reduction in glucose consumption were divided into several groups:hypoxia group,metformin 2 mmol/L group,and 25 g/kg GQD groups treated with 5%,10%,and 15%GQD containing serum.Glucose consumption was used as an indicator of drug efficacy.High⁃resolution liquid chromatography tandem quadrupole time⁃of⁃flight mass spectrometry(UPLC⁃Q⁃TOF⁃MS)was employed to collect metabolite signals from each group.Data were analyzed by using Progenesis QI software,and potential biomarkers were identified through online databases such as HMDB.Finally,metabolic pathways of potential biomarkers were analyzed via the Metabo Analyst 5.0 website.Results An 18 hour hypoxia period was identified as the optimal duration for the replication of the hypoxia⁃induced L02 cell model.GQD containing serums at 5%and 10%significantly increased glucose consumption in hypoxia⁃induced L02 cells after 18 hours.14 biomarkers of hypoxia⁃induced L02 cells were identified,with the levels of 13 biomarkers significantly increased and 1 biomarker significantly decreased.GQD containing serum notably regulated the levels of 3 biomarkers.Conclusion GQD containing serum might improve hypoxia⁃induced abnormal glucose metabolism in L02 cells and enhance glucose consumption by modulating glycero-phospholipid metabolism,glycosylphosphatidylinositol biosynthesis,and sphingolipid metabolism.

关 键 词：葛根芩连汤含药血清 L02细胞 缺氧 糖代谢 代谢组学 

分 类 号：R285.5[医药卫生—中药学]