酸枣仁汤抗焦虑效用及其物质基础的研究

【作者】 谢鸣； 王欣； 王守勇； 朱晓旭； 高琳； 潘思源； 白晶；

【机构】 北京中医药大学；

【摘要】 焦虑症是目前发病率较高的心身疾病之一．现代医学认为本病的发生与个体生物学特征和社会心理因素有关。西医主要应用药物干预的方法,但现有抗焦虑药物存在易依赖、起效缓慢、药物间相互作用和不良反应等诸多缺陷。利用中医方剂多成分共存、多靶点、多途径调节的特点,寻找中药抗焦虑新药具有可能。但引入现代焦虑动物模型和药物效用评价技术．从实验角度揭示中医药防治焦虑症的现代内涵及其作用机制尚属空白。本课题采用目前国际通用的焦虑动物模型和了解到的焦虑病理生理机制,以中医药防治焦虑症的经验以及立法组方思路为背景,选取经典方酸枣仁汤,在确认其抗焦虑作用的基础上,筛选最佳有效剂量,同时探查高架十字迷宫模型(EPM)动物可能存在的内分泌、免疫状态,并从神经-内分泌-免疫网络的角度,在整体、细胞、分子水平上探讨酸枣仁汤抗焦虑作用的可能机制。最后通过对酸枣仁汤的大体部位的分离和分离各部分配伍的正交试验,探察该方抗焦虑效用的物质基础。更多还原

【Abstract】 This subject is based on Chinese medical experience of anti-anxiety.The supposition that classical formula SZRD has effect of anti-anxiety was put forward.The anti-anxiety effect of this preparation (decoction) was found and affirmed.In light of concomitant multiple parts or components within the formula are the fundament of pharmacodynamics,using modern isolation technique and orthogonal experimental design,the anti-anxiety com- ponents and the compatibility were proved after isolating the effect water extract into different parts.The regulation mechanism about the anti-anxiety effects of SZRD in respect of nerve-incretion-immune system and its components were explored in the different levers,such as animal,cell and molecule,focusing on pathology and physiology of anxiety mechanism in modern medicine.The results showed SZRD had anti-anxiety effect and its effective dosage range was from 7.5 to 15g/kg;the material basis of anti-anxiety effect of SZRD are two parts that contain polysac- charide and flavone.SZBD with the effective dosage could decrease the content of NE、DA、5-HT in Hippocam- pus of rat model,increase the content of IL-1_β、GR and GABA-A receptor’s mRNA transcription level in Hypothal- amus and Hippocampus significantly;decrease/increase the concentration of β-EP/CATH、CORT、NO、IL-1_β and TNF-α in serum of rat model.The effective parts of SZRD could increase the content of β-EP in cerebrum of EPM mice and NPY in Nucleus amygdalae of rats,decrease 5-HT content in Hippocampus,improve serum IL-2 content;the drug-contained serum of this formula could resisted the decreased proliferation rate and apoptosis which result from CORT acting on PC12 and the weakening of IL-1β and GR mRNA transcription.The result indicates the anti-anxiety effect of SZRD is related to regulating nerve-incretion-immune net,the mechanism of which is different from that of the classical anti-anxiety drug DZ in western medicine.This subject initiates the method of exploring the material basis of Chinese medicine formula by putting the cut-in point as the relationship between chemical parts of the traditional decoction and particular effect.It may provide a new model for the research in this area which better fits the characteristic of Chinese medicine formula.The components compatibility of anti-anxiety effect of SZRD (with patent in public) gained by the study will provide better basis for further researching new Chinese medicine compounds with anti-anxiety effects with great public profit.Some mechanisms of whole part and the com- ponent compatibility of SZRD will provide scientific evidence for understanding the nourishing Yin clearing away the heat,nourishing the blood and arresting the irritation effects of SZRD from the respect of nerve-incretion-immune system,but for treating anxiety associated with immune disorder.The discover that animal anxiety model induced by elevated plus-maze is accompanied with immune disorder is also significant in更多还原