中藥現(xiàn)代化研究面對的難題

張丹參（中國藥理學會常務理事，中國藥理學會中藥與天然藥物藥理專業(yè)委員會常務委員，河北科技大學教授，主要從事神經(jīng)藥理學和中藥藥理學研究。）

天然產物是發(fā)現(xiàn)新藥的豐富資源，從天然產物中尋找新藥或新的先導化合物，已經(jīng)成為世界新藥研究領域的重要內容。縱觀國內外對中藥進行的研究，目前主要集中在單味藥的研究和方劑的研究?！綨atural products are abundant resources for finding new drugs.Searching for new drugs or new lead compounds from natural products has become an important part of new drug research in the world.The research of TCM is mainly focused on the research of single herbs and the research of compounds in domestic and foreign research.】

應用現(xiàn)代醫(yī)學方法研究中藥復方作用，已有相當長的歷史，但在中藥作用機制研究方面，多數(shù)仍停留在藥效觀察水平。造成這種現(xiàn)象的原因有3個方面，一是成分復雜，目前應用的方法不能對全部（或大部分）成分進行研究和觀察；二是中藥作用機制復雜，是多靶點作用，要全面觀察存在極大困難。雖然有學者提出了有效成分組學的概念，但中藥來源及成分含量的復雜性和多變性導致有效成分及藥效的不穩(wěn)定，是制約中藥現(xiàn)代化研究和應用的瓶頸；三是中藥復方是一個復雜的體系。復方中的每一味藥對于其所包含的化學成分來說，都是一個小復方。【The study on the effects of TCM prescriptions in the application studies medical methods has a long history,but in the research of the mechanism of TCM,most studies still stay at the level of pharmacological effect observa?tion.There are three reasons for this.The first is that the ingredients are complex.The methods in current use cannot study and observe all(or most)components.Second,the mechanism of TCM is complex and has multi-target action.It is very difficultto observe itcomprehensively.Although some scholars have put forward the conceptofeffective compound groups,the complexity and variability of the source and component of TCM lead to the instability of effec?tive components and efficacy,which is the bottle?neck to the research and application of modern?ization of TCM.Third,TCM prescriptions are a complex system.Each drug in the prescription is a small compound for its chemical composition.】

中藥復方的組成，都是以所含生藥量計算。由于種種因素干擾，中藥復方有效成分的含量不均衡，使中藥生藥有效成分的含量不同，導致復方的有效成分含量不均衡，這是中藥研究可比性和可重復性的一個難題?！綯he composition of TCM prescrip?tions is calculated with the amount of crude medi?cine.Due to the interference of various factors,the content of active ingredients in TCM prescrip?trons is not balanced,which leads to the different content of active ingredients of crude drugs,resulting in the imbalance of active ingredients in TCM.This is a difficult problem of comparability and repeatability of TCM research.】

中藥復方的藥理作用是以組成復方的每一味中藥的藥理作用為基礎，而每味中藥的作用又與其有效成分群的作用密切相關。因此，目前的粗制品研究，雖然與傳統(tǒng)臨床用藥方式相符，但由于制劑中有多種成分，成分復雜，這種方法對于闡明中藥的作用機制尚不夠準確；初步分離精制品研究，雖拓展了給藥途徑、便于觀察藥理作用，對開發(fā)中藥的臨床制劑具有重要意義，但由于研究所采取的制備方法各不相同，制劑中所含成分差異較大，不易于進行作用比較?！綯he pharmacological effects of TCM prescriptions are based on the pharmaco?logical effects of each herb in the prescriptions,and the effect of each herb is closely related to its active ingredient group.Although consistent with traditional clinical mode of medication,the current research method on crude product is not accurate enough to clarify the mechanism of action of TCM due to its varietal ingredients and complex compositions.Although the research of preliminary separation of purified products has expanded the routes of administration,made it easy to observe the pharmacological effect and is of great significance for the development of clinical preparations of TCM,the big difference in the composition of the preparation makes mutual comparison of functions difficult due to the different preparation methods adopted in institutes.】

中藥的藥理作用廣泛，使得中藥復方作用多樣化，而同一味中藥在不同配方中的效應不同，決定了其在復方中的作用地位不同，故而有君、臣、佐、使藥之分，通過“君臣佐使”相輔相成發(fā)揮作用。目前，許多中藥及其方劑的研究歷史都比較悠久，這些傳統(tǒng)復方的藥理作用也比較明確，如果依托前期國內外對目標復方的研究基礎，選擇確定適合復方主治的疾病動物模型進行驗證和評價，參考復方各組成的單味藥及其有效成分的藥理作用，合理、適當擴大地選擇有效成分作為研究的有效成分群，盡可能接近復方的原生態(tài)配伍，就可能確定其有效成分群。在中藥復方的藥理作用基礎上，選擇共同作用的靶點，作為目標復方的篩選作用靶點，在高通量篩選模型基礎上，優(yōu)化創(chuàng)新，使之適合目標復方的研究，進一步分析其作用機制，全面評價中藥復方的藥理作用，有可能實現(xiàn)中藥及其復方的大規(guī)?，F(xiàn)代化研究的期望。【The wide pharmacological effects of TCM result in the diversification of the role of TCM prescriptions,while the effect of different herbs of TCM is different in different prescrip?tions,which determine their different roles in the prescription.There are thus"principal,subordi?nate,adjuvant,and guide medicines"in a prescription.All of them work in harmony to make the prescription work.At present,many TCM and their prescriptions have a long history ofresearch,the pharmacologicaleffects of these traditional prescriptions are rather unequivocal.If we are based on the previous studies of the target compound at home and abroad,choose suitable disease animal models for compound indications to verify and appraise,refer to the various pharmacological effects of the single herb and their active ingredients,select more active ingredients as the research group,and get as close as possible to its original ecological compatibility of the compound,it is possible to determine the active ingredient group.Based on the pharmacological effects of TCM prescriptions,we choose the target of common actions as the target of screening target compound.Optimization and innovation on the basis of a high-throughput screening model,butter applicability to the study of the target compound,further analysis of its mechanism,and a compre?hensive evaluation of the pharmacological effects of TCM prescriptions can it make possible to achieve the expectations of large-scale modern?ization research of TCM and its prescriptions.】