基于尿液代谢组学探讨地黄宝源颗粒对糖尿病阴虚热盛证的药效机制  

Exploring the Efficacy and Mechanism of Dihuang Baoyuan Granules on Yin Deficiency and Heat Exuberance Type Diabetes Mellitus Based on Urinary Metabolomics

作　　者：黄瀚辉 孙建辉[1] 李建良 郝莉雨 李绮婧 于泽玥 邓玉荣 李宗源 刘桂敏 霍海如[1] 王奥奥 张宏萌[4] 李洪梅[1] HUANG Hanhui;SUN Jianhui;LI Jianliang;HAO Liyu;LI Qijing;YU Zeyue;DENG Yurong;LI Zongyuan;LIU Guimin;HUO Hairu;WANG Aoao;ZHANG Hongmeng;LI Hongmei(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Shandong University of Traditional Chinese Medicine,Ji'nan 250355,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]中国中医科学院中药资源中心,北京100700 [3]天津中医药大学,天津301617 [4]山东中医药大学,济南250355

出　　处：《中国中医基础医学杂志》2024年第12期2095-2104,共10页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家重点研发计划项目(2023YFF0724803);中国中医科学院科技创新工程项目(CI2021B015);中国中医科学院中药研究所使命导向改革项目(CI2023E001TS01);工业和信息化部2022年产业技术基础公共服务平台项目(2022-230-221)。

摘　　要：目的明确地黄宝源颗粒对糖尿病阴虚热盛证大鼠的药效作用并基于尿代谢组学探讨其作用机制。方法采用高糖高脂饲料饲喂结合链脲佐菌素(streptozocin,STZ)造成2型糖尿病大鼠模型,在此基础上,灌胃附子干姜水提液构建糖尿病阴虚热盛证大鼠模型。连续4周灌胃给予地黄宝源颗粒。检测大鼠空腹血糖、糖化血红蛋白、糖耐量及腺组织病理变化等糖尿病药效作用指标,饮水量、摄食量、血清血栓素B2(TXB2)含量等阴虚热盛证候指标,明确地黄宝源颗粒对糖尿病阴虚热盛证大鼠的药效作用,并结合尿代谢组学分析探讨地黄宝源颗粒对糖尿病阴虚热盛证大鼠的作用机制。结果在药效方面,地黄宝源颗粒能降低大鼠血糖、血清TXB2含量、饮水量、摄食量、糖化血红蛋白含量、糖耐量并改善其胰腺组织病理形态;在机制方面,尿代谢组学提示,与正常组比较,T2DM阴虚热盛组共筛选出936个差异代谢物,地黄宝源颗粒显著回调了其中69个(下调53个,上调16个),地黄宝源颗粒可有效调节糖尿病阴虚热盛证大鼠甘油磷脂代谢、胆汁分泌、类固醇降解、初级胆汁酸生物合成等代谢通路,发挥抗糖尿病阴虚热盛证的作用。结论地黄宝源颗粒能有效改善大鼠糖尿病阴虚热盛证,并调节糖尿病阴虚热盛证大鼠甘油磷脂代谢、胆汁分泌、类固醇降解、初级胆汁酸生物合成等代谢通路。Objective To clarify the pharmacodynamic effect of Dihuang Baoyuan Granules(DHBY)on diabetic rats with Yin deficiency and heat excess,and to explore its mechanism of action based on urinary metabolomics.Methods based on the insulin-resistant type 2 diabetic rat model fed with high sugar and high-fat diet combined with intraperitoneal injection of STZ,the aqueous extract of dried aconite and ginger was intragastric to construct the diabetic rat model of Yin deficiency and heat excess.DHBY was administered by gavage for 4 consecutive weeks.The pharmacodynamic effect indicators of diabetes such as fasting blood glucose,glycated hemoglobin,glucose tolerance,and pathological changes of glandular tissue in rats were detected,and the indicators of Yin deficiency and heat excess syndrome such as water intake,food intake,and serum thromboxane B2(TXB2)content were used to clarify the pharmacodynamic effect of DHBY on Yin deficiency and heat excess diabetic rats,and the mechanism of action of Huang Baoyuan granules on Yin deficiency and heat excess diabetic rats was explored by urinary metabolomics analysis.Results In terms of efficacy,DHBY can reduce blood glucose,serum TXB2 content,water intake,food intake,glycated hemoglobin content,and glucose tolerance and improve the pathological morphology of pancreatic tissue in rats.In terms of mechanism,urinary metabolomics suggested that compared with the normal group,936 differential metabolites were screened out in the T2DM Yin deficiency and heat excess group,and 69 of them were significantly adjusted back by DHBY(53 down-regulated and 16 up-regulated).DHBY can effectively regulate glycerophospholipid metabolism,bile secretion,steroid degradation,primary bile acid biosynthesis,and other metabolic pathways in diabetic rats with Yin deficiency heat excess syndrome,and play a role in anti-Yin deficiency,and heat excess diabetes.Conclusion DHBY can effectively improve diabetic rats with Yin deficiency and heat excess syndrome,and regulate metabolic pathways such as glycerophosphol

关 键 词：地黄宝源颗粒 2型糖尿病 阴虚热盛 尿液代谢组学 

分 类 号：R285[医药卫生—中药学]