当归不同部位功效取向差异的物质基础与药性关联性研究

Angelica Sinensis Radix (ASR), is one of the most commonly used to regulating and nourishing blood in the use of traditional Chinese medicines. Ever since ancient, ASR was divided in three parts from its growing positions, which are head, body, and tail. These three parts erer reported to have different therapeutic activities. And the head, called Guitou in Chinese, is used maily to stop bleeding. The body, named Guishen, which good for regulating and nourishing blood. The tail, named Guiwei, is utilized primarily to promote blood circulation. The whole part of ASR, named Quangui, is thought of promoting and nourishing blood. Based on the guidance and understanding, we try to study the relationship between property and chemical materials of different ASR parts' efficacy orientation. On the basis of previous work, we plan following studies, (1) From the resource system of literature information, we applly suitable data mining technology to explore different parts of ASR' property and syndrome differentiation' rule. (2) Application of coupled chromatography-spectroscopy techniques, different parts of ASR' chemical constituents are separated and analyzed, and variations in the efficacy of material basis can be identified. (3) Activities evaluation and mechanism were conducted from the aspects of whole animal model, tissues (organ) and cells(molecule). (4) On intergration of chemometrics methods Methods and Techniques,we try to nterpret the relativity of different parts of ASR' chemical constituents, property, and efficacy orientation. Through above research, we will reveal the mechanism of different ASR parts' efficacy orientation and rule of applying to disease with syndrome, and provide scientific basis for clinical rational use of different parts of ASR.

当归为补血之要药，历代医家多将当归分头、身、尾应用。基于归头止血、归身补血、归尾活血、全当归活血补血的药性差异，探讨当归不同入药部位功效取向差异的化学物质组成及其药性关联性。课题组在前期研究积累的基础上，拟开展研究工作如下：（1）基于文献信息资源，应用适宜的数据挖掘技术，探讨当归不同入药部位的药性特点及其适应病证的变化规律；（2）利用色谱－质谱多级联用技术，对当归不同入药部位的化学物质进行分离分析，明确其功效差异的化学物质组成特征；（3）从整体、器官、细胞、分子水平多层次揭示当归不同入药部位功效差异的生物学表征与机制；（4）整合化学计量学的方法和技术，阐明当归不同入药部位化学物质组成-药性-功效取向差异的关联性。通过以上研究，揭示当归不同入药部位功效取向差异机理及其应用病证的变化规律，为当归不同入药部位的临床科学合理用药提供科学依据。

当归为补血之要药，历代医家多将当归分头、身、尾应用。基于归头止血、归身补血、归尾活血、全当归活血补血的药性差异，探讨当归不同入药部位功效取向差异的化学物质组成及其药性关联性。课题组开展了下列研究：（1）基于文献信息资源，应用适宜的数据挖掘技术，探讨当归不同入药部位的药性特点及其适应病证的变化规律；（2）通过主成分分析综合评分法，对其不同商品等级药材化学质量进行评价分析。发现当归的商品等级与其化学指标含量不成简单正负比例关系，现行市场商品规格中三等品当归有效成分含量相对较高。研究结果有助于揭示当归商品等级划分的科学依据。（3）利用UPLC-Q-TOF-MS等方法，测定了60批不同部位当归药材中29种化学成分的含量。ANOVA分析结果显示：阿魏酸、丁基苯酞在归尾中含量较高，藁本内酯的含量，在归身中比归头和归尾中显著较低，洋川芎内酯H、洋川芎内酯I、洋川芎内酯A则从头部向尾部含量逐渐减少。大多数氨基酸和核苷在当归药材中分布规律相似，在归头比归尾含量高。分析结果显示了不同部位当归药材化学成分的化学组成特点及差异性。（4）建立了适宜于当归药材止血、补血、活血的药效试验模型。结果显示：当归头临床等效剂量（1.5g生药/kg）组即表现出显著止血效应，而当归尾以及全当归各剂量组均未观察到显著的止血作用。当归身和全归高剂量组对血虚小鼠有显著补血作用（P<0.05），当归身的补血作用比全归略强，但均弱于对照组。当归头和当归尾各剂量组均未见显著补血作用。当归尾、全当归的活血化瘀作用显著，且当归尾略强于全归，而当归身和当归头组均未观察到显著的活血化瘀作用。而当归尾和全归仅6.00 g生药/kg（相当于6倍临床等效剂量）剂量组表现出显著的抗凝作用（P<0.05），二者作用强度相当，当归其他各个部位均未观察到显著的抗凝作用。（5）采用灰色关联分析法，对当归不同入药部位化学物质组成和功效指标进行分析，探讨当归不同部位化学成分与功效取向差异的关联性。灰色关联度分析结果显示，本课题组选用的止血、活血、补血效应指标与当归不同部位化学成分差异具有较高的关联性，当归不同部位化学成分含量的差异是影响当归不同功效的物质基础，也是影响其药性差异的重要因素。本研究结果揭示当归不同入药部位化学成分与功效取向差异机理，为当归不同入药部位的临床科学合理用药提供科学依据。