基于代谢组学研究生地黄对寒证大鼠的药性  

Medicinal properties of Rehmanniae Radix in rats with cold syndrome based on metabolomics

作　　者：张文森 崔娜 苏发智 张转转 贾晨宸 孙延平[1] 杨炳友[1] 匡海学[1] 王秋红[2] ZHANG Wensen;CUI Na;SU Fazhi;ZHANG Zhuanzhuan;JIA Chenchen;SUN Yanping;YANG Bingyou;KUANG Haixue;WANG Qiuhong(Key Laboratory of Basic and Applied Research of Beijing Medicine,Ministry of Education,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Guangdong Engineering Technology Research Center for Standardized Processing of Traditional Chinese Medicine Pieces,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]黑龙江中医药大学教育部北药基础与应用研究重点实验室,黑龙江哈尔滨150040 [2]广东药科大学广东省中药饮片规范化炮制工程技术研究中心,广东广州510006

出　　处：《中草药》2024年第7期2237-2247,共11页Chinese Traditional and Herbal Drugs

基　　金：国家中医药管理局中医药传承与创新“百千万”人才工程-岐黄工程首席科学家支持项目(国中医药人教函[2021]7号);国家中医药管理局中医药传承与创新“百千万”人才工程(岐黄工程)岐黄学者支持项目(国中医药人教函[2018]284号);2022年全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号);第七批全国老中医药专家学术经验继承工作项目(国中医药人教函[2022]76号);黑龙江省“头雁”团队支持项目(黑龙江省头雁行动领导小组文件[2019]5号)。

摘　　要：目的确定生地黄Rehmanniae Radix的性味功效物质基础,阐明生地黄及其拆分组分的寒热药性归属以及中药药性的内部精细结构。方法采用水煎煮法、水提醇沉法和色谱分离技术,对生地黄的主要化学成分进行拆分。在建立寒证大鼠模型的基础上,测定与能量代谢和物质代谢密切相关的生理生化指标。同时,对大鼠尿液进行代谢组学分析,筛选出各给药组大鼠尿液中的差异代谢物,从而确定潜在的生物标志物和代谢通路。结果水煎液、多糖、环烯醚萜苷对寒证模型大鼠呈现相同的药性作用倾向,均能降低肝组织Na^(+),K^(+)-三磷酸腺苷(adenosine triphosphate,ATP)酶活性和血浆中三碘甲状腺原氨酸(3,5,3′-triiodothyronine,T_(3))、甲状腺素(thyroxine,T_(4))、丙酮酸(pyruvic acid,PA)、多巴胺(dopamine,DA)、去甲肾上腺素(norepinephrine,NE)的水平及琥珀酸脱氢酶(succinate dehydrogenase,SDH)活性,升高血浆中乙酰胆碱酯酶(acetylcholinesterase,AchE)活性。低聚糖对寒证模型大鼠呈现相反的药性作用倾向,能升高大鼠肝组织Na^(+),K^(+)-ATP酶活性和血浆中T3、T4、PA、DA、NE的水平及SDH活性,降低血浆中AchE活性。结论水煎液、多糖、环烯醚萜苷抑制能量代谢和物质代谢,具有寒凉性;低聚糖促进能量代谢和物质代谢,具有温热性。Objective To determine the material basis of the properties,taste and efficacy of Dihuang(Rehmanniae Radix,RR),and to clarify the cold and heat properties of RR and its separated components,as well as the internal fine structure of each traditional Chinese medicine.Methods By using water decoction,water extraction and alcohol precipitation and chromatographic separation techniques,the main chemical components of RR were separated.On the basis of establishing a rat model of cold syndrome,the physiological and biochemical indicators closely related to energy metabolism and material metabolism were measured.At the same time,metabolomic analysis was performed on rat urine to screen out differential metabolites in the urine of rats treated with each drug,thereby identifying potential biomarkers and metabolic pathways.Results Decoction,polysaccharides and iridoid glycosides showed the same medicinal effect tendency on cold syndrome model rats,and they could reduce Na^(+),K^(+)-adenosine triphosphate(ATP)activity in liver and levels of 3,5,3′-triiodothyronine(T_(3)),thyroxine(T_(4)),pyruvic acid(PA),dopamine(DA),norepinephrine(NE)and succinate dehydrogenase(SDH)activity in plasma,and increase acetylcholinesterase(AchE)activity in plamsa.Oligosaccharides showed opposite medicinal effects on cold syndrome model rats,and could increase Na^(+),K^(+)-ATPase activity in liver and levels of T3,T4,PA,DA,NE and SDH activity in plasma of rats,and reduce AchE activity in plamsa.Conclusion Decoction,polysaccharide and iridoid glycosides inhibit energy metabolism and material metabolism,and have cold and cooling properties;Oligosaccharides promote energy metabolism and material metabolism,and have warming properties.

关 键 词：药性 代谢组学 物质代谢 能量代谢 生地黄 棉子糖 蔗糖 水苏糖 

分 类 号：R285.5[医药卫生—中药学]