生物钟基因:中药作用的新靶点

Circadian clock genes:New targets of traditional Chinese medicine

中医学早在两千多年前就已经提出了"择时给药"和"因时制宜"的理念。这一理念与现代的时间药理学、时间毒理学、时间治疗学不谋而合。现代时辰药理学研究发现生物钟不仅影响药物的吸收、分布、代谢和排泄,而且还与药物的治疗作用和毒性密切相关。生物钟是生物适应环境周期性变化的一种内在机制,存在于中枢和外周组织以及细胞中。生物钟系统由核心基因(Clock、Bmal1和Npas2)、负反馈基因(Cry和Per)、钟控基因和靶基因(Dbp、Rev-Erbα、Rorα、Csnk、Temless等)组成。有研究显示,在分子生物学水平上,中药和中药复方可通过影响生物钟基因发挥治疗作用,因此,中药与生物钟之间存在相关性。文章对此做一综述,以期为中药作用的多靶点提供新思路。

Chronopharmacology has been recognized by traditional Chinese medicine(TCM) since ancient times.This concept coincides with modern time pharmacology,time toxicology and time therapy.Accumulating evidence showed that circadian clock not only affects drug absorption,distribution,metabolism,and excretion,but also affects efficacy and toxicity of drugs.Circadian clock is an innate mechanism for human beings to adapt periodic changes of the environment,and exists in brain,peripheral tissues and cells.The circadian clock consists of core clock genes(Clock,Bmal1 and Npas2),negative feedback genes(Cry and Per),clock target and controlled genes(Dbp,Rev-Erbα,Rorα,Csnk,Temless,etc.).On the level of molecular biology,TCM could influence the expression of clock genes to treat diseases including the brain diseases,metabolic diseases,cardiovascular disease,cancer and aging.Therefore,there are associations of TCM with circadian clock,and clock genes could be a therapeutic target of TCM.This paper reviewed the progress in this field.