Development of Chronotherapy Based on Clock Genes

哺乳动物昼夜节律起搏器位于成对的视交叉上核(SCN)。时钟基因是控制生理和行为昼夜节律的基因。许多药物的有效性和毒性取决于给药时间的不同，这些时间与生物钟控制下的生化、生理和行为过程的24小时节律有关。然而，许多药物仍然是不分时间给药的。找出用于选择给药时间的节律标记物将促进时辰药物治疗的进展和推广。在本研究中，澄清了以下几点。监测节律标志物可能有助于选择一天中最合适的给药时间，以提高其疗效和/或减少其副作用。此外，我们还显示了干扰素对运动节律、体温和外周和SCN中时钟基因mRNA表达的干扰作用。时钟功能的改变是一个新的不良反应的概念，可以通过设计一种给药方案来克服这种改变，从而将药物对时钟功能的不良影响降至最低。此外，通过改变摄食时间或几种药物的节律性给药来控制生活器官的状况，从而产生新的节律性，可能会导致时辰药物治疗的新概念。

Mammal ians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. In the present study, the following points were clarified. To monitor the rhythmic marker may be useful to choose the most appropriate time of day for administration of drugs that may increase their therapeutic effects and/or reduce their side effects. Also, we showed the disruptive effect of interferon on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, can be overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs maylead to the new concept of chronopharmacotherapy.