理虚解郁方及各方药组分对CFS生物节律基因及HPA轴效应激素调控靶点的研究

The physical and mental fatigue of Chronic Fatigue Syndrome (CFS)performance excitement-inhibition disorder,the excitement-inhibition disorders are closely related to the Biological Rhythm Genes of hypothalamic suprachiasmatic nucleus(SCN)and the changes of circadian rhythm in hypothalamic-pituitary-adrenal axis (HPA axis).A preliminary study confirmed that LI XU JIE YU adjust the disorders of biological rhythms of CFS,so research group proposed the hypothesis-the effective components of LI XU JIE YU did multi-link and multi-target effect in CFS,it is related to the Biological Rhythm Genes of hypothalamic suprachiasmatic nucleus (SCN)and the changes of circadian rhythm in hypothalamic-pituitary-adrenal axis (HPA axis).we would like to do animal experiments to research LI XU JIE YU and divide LI XU JIE YU into improving Qi and spleen group,resolving phlegm and fragrant group, promoting blood and circulation and soothe the nerves group , LI XU JIE YU group by the efficacy of traditional Chinese medicine. Around the study site of the SCN gene (CLOCK, of BMAL1, of Per1-3 and Cry1-2) and CORT circadian rhythms law in the hypothalamus and serum corticosterone of HPA axis,We would like to clarify the exact role of target of prescription components in LI XU JIE YU by the way of Chronobiology,to explore the effect substances that play a basic role in LI XU JIE YU,to discuss the integration effect mechanism of LI XU JIE YU,and to provide scientific content of the theory of Prescription and law of compatibility.

慢性疲劳综合征(CFS)躯体和精神疲劳是兴奋-抑制紊乱的表现，与下丘脑视交叉上核（SCN）中生物节律基因及反馈回路、HPA轴昼夜节律的改变关系密切。前期研究已证明理虚解郁方能有效调整CFS紊乱的生物节律，为此课题组提出假说--理虚解郁方中有效中药组分多环节、多靶点的整合效应与调整SCN中节律基因、反馈回路及HPA轴的节律有关。拟将复方按功效分为益气健脾、化痰解郁、和血安神及两两功效协同组和综合组共七组，通过动物实验进行各中药组分功效研究，围绕SCN中生物调节基因（CLOCK, BMAL1, Per1-3和Cry1-2）及HPA轴中下丘脑、血清皮质酮CORT昼夜节律规律等研究点，采用时间生物学的方法进一步明确理虚解郁方的各种方药组分的确切作用靶点，探寻复方发挥作用的基础效应物质，深入探讨理虚解郁方整合效应机制，为理虚解郁方的组方理论、配伍规律等提供科学内涵。

慢性疲劳综合征(CFS)躯体和精神疲劳是兴奋-抑制紊乱的表现，与下丘脑视交叉上核（SCN）中生物节律基因及反馈回路、HPA轴昼夜节律的改变关系密切。前期研究已证明理虚解郁方能有效调整CFS紊乱的生物节律，为此课题组通过对理虚解郁方中有效中药组分研究，观察与SCN中节律基因及HPA轴的节律的关系。实验将复方按功效分为益气健脾、化痰解郁、和血安神及两两功效协同组和综合组共七组，通过动物实验进行各中药组分功效研究，通过多重复合应激致慢性疲劳模型，观测大鼠认知行为的变化，验证理虚解郁综合方对其认知的改善作用；围绕SCN中生物调节基因（CLOCK, BMAL, Per和Cry）、血清皮质酮CORT、体温等昼夜节律规律等研究点，采用时间生物学的方法探讨理虚解郁方的各种方药组分的作用。研究结果提示，理虚解郁方能明显改善CFS模型大鼠躯体及精神疲劳，增加旷场实验直立及穿格次数，缩短悬尾试验静止时间，延长模型大鼠力竭游泳时间、缩短水迷宫实验寻找平台时间，以益气健脾组C1组、益气健脾+化痰解郁C4组作用明显。理虚解郁方能明显改善血浆CORT、SCN生物调节基因（CLOCK, BMAL1, Per1和Cry1）的生物节律，另中药C1组、C4组、C5组能调节血浆CORT的昼夜节律，中药C4组、C5组能调节CLOCK基因昼夜节律;中药C1组、C4组能调节BMAL1基因昼夜节律;中药C3组能调节Per1基因昼夜节律,中药C1组能调节Cry1基因昼夜节律，实验结果证明理虚解郁方能改善CFS模型大鼠躯体及精神疲劳，调节血浆CORT、SCN节律基因生物节律，不同方药组分作用于不同靶点，共同发挥调节慢性疲劳综合征紊乱生物节律的作用。