基于“中药性（气）与能量代谢相关性”的人参类中药不良反应机制及物质基础研究

The ginseng Chinese drugs (GCDs) referred to the ginseng (sun-dried ginseng, slightly warm nature), red ginseng (warm nature), American ginseng (cool nature) and ginseng leaves (cold nature), which recorded in the China’s Pharmacopoeia. Their consumptions are huge, especially, cultivated ginseng was approved to be used as food materials by the State Food and Drug Administration in 2012. Recently, the reports for the adverse drug reaction (ADR) caused by taking these drugs and their products are also gradually increasing, such as fireness caused by ginseng. Thus, it is necessary to sudy the ADR mechanism and constituents of GCDs. Ginsenosides are regarded as one of main active ingredients of the GCDs, but their types and proportions are distinctive in the four drugs and these drugs exhibited different natures are all belonged to qi-tonifying drugs. Followed with the newer scientific research results on the nature of Chinese drugs and based on the new viewpoint of “correlation between the nature of Chinese drugs and energy metabolism of organism” as an entry point for the project, previously, we firstly discovered that the ADRs of GCDs were associated with the inhibitory effect on the activity of liver Na+-K+-ATPase. Further, the dynamic correlation analysis of “Nature-Fingerprint-Effect-ADRs-Biochemical Indexes related to energy metabolism” of the four drugs with the help of metabolomic technique, will elucidate the ADR forming mechanism of GCDs and their substantial basis. The research will lay foundation for the reasonable application of GCDs, detoxification with ginseng composite, elucidation of the relationship between the nature of Chinese drugs and their effects and ADR as well as the deeper recognition of essential attribute of the nature of Chinese drugs. The project will fill in the research blank in this field.

人参类中药是指《中国药典》中收录的人参（生晒参、性微温）、红参（性温）、西洋参（性凉）和人参叶（性寒）。它们消费量均较大，尤其2012年国家批准栽培人参还可作为食品原料。近年来，这些中药使用中的不良反应如“上火”等的报道也逐渐增多，对其不良反应形成机制及成分进行研究具有一定现实意义。人参皂苷为这些中药的主要有效成分之一，但在不同中药中的种类和比例不同；均作为补气药，但性气差别较大。项目跟踪有关中药性气的较新研究成果，前期基于“中药性气与能量代谢相关性”作为切入点，发现人参类中药的不良反应均与其抑制肝Na+-K+-ATP酶活力相关，进一步通过对这四种中药“性-谱-效-不良反应-能量代谢相关生化指标”动态关联分析，辅以代谢组学手段，阐明人参类中药不良反应形成机制及物质基础。项目为人参类中药合理安全使用、配伍减毒、阐明人参类中药性气与其功效及不良反应关系以及加深对中药性气的本质属性认识奠定基础。

人参类中药是指《中国药典》中收录的人参（生晒参、性微温）、红参（性温）、西洋参（性凉）和人参叶（性寒）。近年来，由于五年生以下人参（主要是园参）被批准为食品新资源，食用人参引起“上火”的不良反应也越来越引起人们重视。课题的总体目标是基于“中药性气与能量代谢相关性”作为切入点，通过对这四种中药“性-不良反应-能量代谢相关生化指标”动态关联分析，辅以代谢组学和微生物群落变化分析手段，阐明人参“上火”不良反应形成机制及物质基础。研究根据动物给药后表观指标的动态变化（尤其是唾液分泌量、心率等）以及与能量代谢相关指标，辅以代谢组学及菌群多样性变化分析来阐明人参类中药不良反应动态形成机制。结果表明人参高剂量组在给药两周后出现动物唾液分泌量降低、体温升高等“上火”症状，且呈现微温药性人参最明显。人参类中药对下丘脑-垂体-肾上腺（HPA）和下丘脑-垂体-甲状腺轴（HPT）的影响特征是先促进，后降低，即在给药第二周和第三周时肾上腺皮质激素、甲状腺素水平及肝的Na+-K+-ATP酶活力达到最高，然后逐步下降。进一步我们探讨了人参类中药不良反应与物质代谢以及菌群多样性变化的相关性。进一步通过组分拆分，我们发现人参中引起“上火”的物质主要是其多糖和小极性组分（主要为次生皂苷），这也是人参的主要活性成分。我们进一步基于生物信息学技术结合细胞和酶的评价方法，建立单体皂苷的性气评价方法。以呈现温热性气的人参皂苷-Rg3为例，对其不良反应进行研究，发现其呈现的“上火”特征与人参“上火”特征一致。以上研究结果表明人参温热性气虽对人参“上火”副作用有一定贡献，更确切地说人参“上火”应为其补气作用引起的副作用，且与剂量有较大关系。项目为人参类中药合理安全使用和阐明人参类中药性气与其功效及不良反应关系以及加深对中药性气的本质属性认识奠定基础。研究发表相关论文15篇，其中SCI收载论文6篇。