青黛对2,4-二硝基苯酚诱导发热大鼠模型的解热活性及潜在机制研究  

Antipyretic activity and potential mechanism of Indigo Naturalis on 2,4-dinitrophenol-induced fever rat model

作　　者：徐小蓉 唐进法[2] 张辉[2] 冉飞 廖维 王芳 阳向波 林俊芝 杨明 张定堃[1] 韩丽[1] XU Xiao-rong;TANG Jin-fa;ZHANG Hui;RAN Fei;LIAO Wei;WANG Fang;YANG Xiang-bo;LIN Jun-zhi;YANG Ming;ZHANG Ding-kun;HAN Li(State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;Yaan Xunkang Pharmaceutical Co.,Ltd.,Yaan 625600,China;Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China)

机构地区：[1]成都中医药大学药学院中药资源系统研究与开发利用省部共建国家重点实验室培育基地,四川成都611137 [2]河南中医药大学第一附属医院,河南郑州450000 [3]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [4]雅安迅康药业有限公司,四川雅安625600 [5]成都中医药大学附属医院代谢性疾病中医药调控四川省重点实验室,四川成都610072

出　　处：《中国中药杂志》2021年第13期3205-3212,共8页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2018YFC1707205);国家自然科学基金面上项目(81773918);四川省科技厅杰出青年科技人才项目(2019JDJQ0007);江西中医药大学创新药物与高效节能降耗制药设备国家重点实验室开放基金课题项目(GZSYS202003);成都中医药大学西南特色中药资源重点实验室开放基金项目(2020XSGG020)。

摘　　要：青黛作为一种有效的清热药在中医药领域具有悠久的应用历史。其中有机物质量分数约10%,主要包括靛蓝、靛玉红。但其解热物质成分与机制尚未完全阐明。该研究以直肠温度变化为指标研究了青黛对2,4-二硝基苯酚发热大鼠的解热成分与解热作用。采用ELISA试剂盒测定下丘脑中PGE_(2)、cAMP的含量,血清中TNF-α、IL-1β和IL-6的含量,并结合UPLC-QTOF-MS对发热大鼠的血浆样本进行了代谢组学分析研究,探索潜在的生物标志物,并对青黛及其有效成分的解热机制进行探讨。结果表明,与发热模型大鼠相比,经青黛、有机物、靛蓝、靛玉红治疗后大鼠直肠温度的上升趋势在0.5 h后得到抑制(P<0.05),其中青黛、有机物解热效果最好。ELISA检测表明,有机物、靛蓝均能抑制PGE_(2)、cAMP(P<0.01)的表达。青黛、有机物能抑制TNF-α(P<0.05)的上升,从青黛组、有机物组、靛蓝组、靛玉红组的血浆样本中共鉴定出21种内源性代谢物,主要涉及甘油磷脂代谢。As an effective antipyretic medicine,Indigo Naturalis has a long history of application in the field of Chinese medicine.The content of organics,mainly indigo and indirubin,is about 10%.However,the active ingredients and mechanism of its antipyretic effect have not yet been fully elucidated.In view of this,they were investigated in this study with the rectal temperature change as an indicator and 2,4-dinitrophenol-induced fever rats as subjects.The content of PGE2 and c AMP in the hypothalamus and the serum levels of TNF-α,IL-1βand IL-6 were determined by ELISA.Moreover,the plasma samples of fever rats were analyzed by metabonomics in combination with UPLC-Q-TOF-MS for the exploration of potential biomarkers and the discussion on the antipyretic mechanism of Indigo Naturalis and its active ingredients.The results showed that the rising trend of rectal temperature in rats was suppressed 0.5 h after the treatment with Indigo Naturalis,organic matter,indigo or indirubin as compared with the rats of model group(P<0.05),among which Indigo Naturalis and organic matter had better antipyretic effect.ELISA results showed that organic matter and indigo can inhibit the expression of PGE2 and c AMP(P<0.01),while Indigo Naturalis and organic matter were effective in curbing the increase in TNF-α(P<0.05).A total of 21 endogenous metabolites were identified from the plasma samples of the Indigo Naturalis,organic matter,indigo and indirubin groups,which were mainly involved in glycerophospholipid metabolism.

关 键 词：青黛 解热 成分 细胞因子 非靶向代谢组学 

分 类 号：R285.5[医药卫生—中药学]