表观代谢调控——中医药调控人体稳态研究的新方向

Epi-Metabolism Regulation:a New Direction of Traditional Chinese Medicine Study in Regulating Human Homeostasis

代谢稳态是机体重要的平衡体系,包括物质合成平衡、能量代谢平衡。表观代谢物为一种脱离经典功能的代谢物,由经典代谢物在酶错误或化学损伤情况下,发生简单的、可逆转的结构修饰而生成,这种修饰反应参与多种疾病过程之中。因而,经典代谢物与表观代谢物之间的修饰/脱修饰反应可以看作是机体一种新的代谢稳态。调控表观代谢稳态可能是中医药治疗机制中的重要环节,而发展中医药表观代谢调控理论的困难主要在于方法学。表观代谢调控在现代医学研究中仍是一个新课题,缺乏完善的研究体系,虽然有些质谱数据库涵盖了表观代谢产物,但这些信息多是基于结构预测,缺乏实验证实,目前也没有可获得的标准品进行结构确证。同时,表观代谢产物往往浓度极低,如何提高检测方法的灵敏度也亟待解决。因此,构建系统的中医药表观代谢调控研究策略应该包括以下方面:(1)完善表观代谢产物质谱数据库,以便能够在非靶向代谢组学方法中找到中医药调控的表观代谢标记物。(2)为了提高检测灵敏度,可以通过合成和结构修饰的方法得到目标表观代谢产物,构建靶向代谢组学方法,或者基于非靶向代谢物鉴定结果,建立拟靶向分析方法。(3)通过结合转录组学、蛋白组学或生物信息学手段,分析中医药表观代谢调控的分子网络,定位关键调节酶,进而确定其作用靶点。

Metabolic homeostasis is an important balance system in the body,including material synthesis balance and energy metabolism balance.An epigenetic metabolite is a type of metabolite that deviates from its classical function and is generated by simple and reversible structural modifications of classical metabolites in the event of enzyme errors or chemical damage.This modification reaction is involved in various disease processes.Therefore,the modification/unmodification reaction between classical and epigenetic metabolites can be regarded as a new metabolic homeostasis in the body.Regulating epigenetic metabolic homeostasis may be an important link in the treatment mechanism of traditional Chinese medicine,and the difficulty in developing the theory of epigenetic metabolic regulation in traditional Chinese medicine mainly lies in methodology.The regulation of epigenetic metabolism is still a new topic in modern medical research,lacking a comprehensive research system.Although some mass spectrometry databases cover epigenetic metabolites,most of this information is based on structural prediction and lacks experimental confirmation.Currently,there are no available standard substances for structural confirmation.Meanwhile,the concentration of apparent metabolites is often extremely low,and it is urgent to improve the sensitivity of detection methods.Therefore,for the construction of a systematic research strategy for the regulation of traditional Chinese medicine epigenetic metabolism,the following aspects should be included:(1)Improving the mass spectrometry database of epigenetic metabolites,so that the epigenetic metabolic markers regulated by traditional Chinese medicine can be found in non targeted metabolomics methods.(2)In order to improve detection sensitivity,target epigenetic metabolites can be obtained through synthesis and structural modification methods,and targeted metabolomics methods can be constructed.Alternatively,based on the identification results of non targeted metabolites,targeted analysis methods can be established.(3)By combining transcriptomics,proteomics,or bioinformatics methods,analyze the molecular network of TCM epigenetic metabolism regulation,locate key regulatory enzymes,and determine their targets of action.