基于药性构成“三要素”数理分析模式的中药寒热药性生物学表征差异研究

Study of biological performance of Chinese materia medica with either a cold or hot property based on the three-element mathematical analysis model

目的:中药药性是中药作用于不同状态机体的,与化学成分相关的生物学效应的概括和归纳。中药药性研究需要从化学成分要素、机体状态要素和生物效应要素及其关联关系进行系统探讨。本研究遵循中药临床应用特点,旨在引入数学思想和方法建立"三要素"数理分析模式,并基于该模式研究中药寒热药性,探讨寒热药性生物学表征差异。方法:借鉴中药的病态选择活性概念,基于数学上交互作用的思想,将化学成分要素和机体状态要素的作用统一于生物学效应量中。在此基础上,通过效应分解、强度计算、频数统计、关联度分析等步骤并结合散点图,形成"三要素"数理分析模式。设计并实施热性药附子、肉桂和寒性药黄柏、栀子(化学成分要素)干预正常状态、糖皮质激素诱导的虚寒和虚热状态(机体状态要素)大鼠的比较药理学实验(生物效应要素),运用该模式对实验结果进行数理分析。数理分析结果以散点图形式输出,通过计算药物干预虚寒、虚热两种状态的生物效应点在"药效区"和"毒性区"的频数分布,结合关联度分析,可以对比不同药物的寒热药性表达程度。结果:干预虚寒状态后"药效点"与干预虚热状态后"药效点"的频数比,附子为7∶3、肉桂为3∶3、黄柏为4∶4、栀子为1∶5;干预两种状态后"毒性点"的频数和,附子为4、肉桂为0、黄柏为2、栀子为4。关联度分析显示,"附子、肉桂、黄柏、栀子"与"适用于虚寒状态、适用于虚热状态"呈正相关。即,按照附子、肉桂、黄柏、栀子的顺序,热性越来越弱,寒性越来越强。同时,对于上述4味药,药效越明显,则毒性越明显。结论:本研究采用的基于药性构成"三要素"理论的数理分析模式能够有效阐释寒热药性的生物学表征差异,为中药药性理论的现代解读提供理论依据和数学工具,为中药药性实质研究奠定基础。

Objective：The properties of Chinese materia medica are believed to be the summarization of the effects of biological performance on the various body states.Systemic discussion of chemical-factor elements,body-condition elements,biological-performance elements and their interrelationships is needed for research into the properties of Chinese materia medica.Following the practical characteristics of Chinese medicine,the three-element mathematical model was formed by introducing some mathematical concepts and methods and was used to study the cold or hot property of Chinese medicine,and to investigate the difference in biological performances of the two properties.Methods：By using the concept of different functionality of Chinese medicine on abnormal states and the idea of interaction in mathematics,the effects of chemical-factor elements and body-condition elements were normalized to the amount of biological performance which was represented by some important indicators.The three-element mathematical model was formed with scatter plots through four steps,including effect separation,intensity calculation,frequency statistics and relevance analysis.A comparison pharmacology experiment of administration of hot property medicines,Fuzi（Radix Aconiti Lateralis Preparata）and Rougui（Cortex Cinnamomi）,and cold property medicines,Huangbai（Cortex Phellodendri）and Zhizi（Fructus Gardeniae）on normal and glucocorticoid-induced yang-deficiency and yin-deficiency states was designed.The results were analyzed by the mathematical model.The scatter plots were the main output of model analysis.The expression of cold property and hot property was able to be quantified by frequency distribution of biological indexes of administrations on yang-deficiency and yin-deficiency states in the ＂efficacy zone＂ and ＂toxicity zone＂ of the plots and by the relevance analysis.Results：The ratios of biological indicator frequency in the ＂efficacy zone＂ of administrations on yang-deficiency state and yin-deficiency state were 7∶3 for Fuzi,3∶3 for Rougui,4∶4 for Huangbai and 1∶5 for Zhizi.The sums of the biological indicator frequency in the ＂toxicity zone＂ of administration on the two states were 4 for Fuzi,0 for Rougui,2 for Huangbai and 4 for Zhizi.The relevance analysis showed that the order from Fuzi,Rougui,Huangbai to Zhizi was proportional to the change from ＂be true of yang-deficiency state＂ to ＂be true of yin-deficiency state＂.The extent of the hot property decreased while that of the cold property increased in the order of Fuzi,Rougui,Huangbai and Zhizi.The stronger the efficacy of above medicines is,the more obvious the toxicity displayed.Conclusion：The three-element mathematical model employed in this study is effectively capable of explaining the different biological expressions between hot property medicines and cold property medicines.This suggests that it may provide a mathematical tool and theoretical basis for the modern interpretation of cold property and hot property of Chinese medicine,and provide new ideas for further studing into the essence of Chinese medicine property theory.