CN107247867B - 一种中药效应化学标志物群的辨识方法 - Google Patents
一种中药效应化学标志物群的辨识方法 Download PDFInfo
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- CN107247867B CN107247867B CN201710339006.5A CN201710339006A CN107247867B CN 107247867 B CN107247867 B CN 107247867B CN 201710339006 A CN201710339006 A CN 201710339006A CN 107247867 B CN107247867 B CN 107247867B
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Abstract
本发明公开了一种中药的效应化学标志物群的辨识方法，该方法包括以下步骤：获取中药中各化学成分的种类和含量；选取所述中药治疗复杂性疾病的主要作用途径，获取各化学成分在治疗复杂性疾病中的校正药效得分值；选择能够体现中药整体生物效应的化学成分组合作为潜在效应化学标志物群；通过验证实验，判断所述潜在效应化学标志物群是否为效应化学标志物群。本发明不仅考虑中药中各成分的含量，还考虑了各成分对于疾病治疗各作用途径的作用，能够较全面地辨识出中药中发挥治疗作用的效应化学标志物群，为应用效应化学标志物群进行相关中药的质量评价、质量控制、作用机制以及相关中药的二次开发和中药新药的创制提供了基础。
Description
技术领域
本发明涉及医药领域，尤其涉及一种中药的效应化学标志物群的辨识方法。
背景技术
中医药是中华民族数千年来在生活实践和与疾病斗争的过程中积累的瑰宝，是在几千年临床实践中逐步发展而成的医学科学，直至今日仍在国民健康事业中具有举足轻重的作用，同时也为全人类的健康做出了重要贡献。
中药及植物药的化学组成复杂，且常通过多成分、多靶点整合调节。为体现中药的这一特点，目前中药及植物药质量评价的方式已逐渐从单指标成分向多指标成分检测控制转变。然而，如何从中药众多的成分中选取能反映中药整体作用的成分群，并进而用该成分群进行中药质量评价是亟需解决的难题。
中药的“效应化学标志物群”，被定义为中药中具有与全方药效相当的化学成分组合，其可用于评价中药质量，并可进一步用于中药质量的控制。该概念的提出为中药的质量评价、质量控制提供了一个新的思路。
目前，国内外中药药效物质发现研究方法主要分以下几种模式。
1)中药药效物质的系统分离筛选法。通过柱色谱、薄层色谱等多种技术分离得到中药中的成分，通过动物、细胞和分子等药理模型测试，发现其中的活性成分。该方法在较长一段时间内是药效物质发现的主要方法，但存在操作繁琐，实验周期长，且结果不确定性高的缺点。
2)活性导向的中药药效物质发现方法。又称活性示踪法，其以目标活性为导向，进行针对性的分离制备，加快了中药药效物质发现的速度。但常出现越纯化活性越差的现象，甚至无法得到有效的单体。
3)血清药物化学和血清药理学方法。随着血清药理学和血清药物化学的提出，研究者们开始关注中药口服后的入血成分，并将其视为潜在药效物质(文献1-3)。实际研究中存在种属间结果差异等局限性。
4)中药药效物质的快速发现方法。随着分子生物学和分析化学方法技术的发展，研究者们(文献4-14)通过生物膜色谱、亲和选择色谱等化学生物学方法结合液质联用等技术在中药活性物质筛选与鉴定方面开展了系列尝试，逐渐发展形成了针对特定靶标的中药药效物质快速发现方法。
然而，现有的药效物质发现方法常专注于发现高活性的成分，而较少考虑成分含量对其在中药药效发挥的重要性。中药中各活性成分往往含量差异悬殊，有学者提出，明确中药中各活性成分的含量是深入探讨中药药效物质及作用机制的基础。中药“定量组效关系”重视研究中药中各成分含量与药效的关系，但该法常以单个靶点、单一活性评价药效，与中药多靶点的作用特点不符；如以整体动物评价药效则工作量巨大，且存在药效指标灵敏度低，难以反映组分变化带来的活性差异等问题。
注射用血塞通是临床常用的治疗心脑血管疾病药物，如何寻找注射用血塞的效应化学标志物群是本领域的一个研究方向。
发明内容
本发明提供了一种中药的效应化学标志物群的辨识方法，该方法能够准确获得与中药全方药效相当的化学成分组合。
1、一种中药效应化学标志物群的辨识方法，包括以下步骤：
(1)获取中药中各化学成分的种类和含量；
(2)选取所述中药治疗复杂性疾病的主要作用途径，并根据所述作用途径，获取各化学成分在作用复杂性疾病中的校正药效得分值；
a)从已公开文献的实验数据中，计算得到回调率RR；
RR＝(M-D)/(M-N) (1)；
式(1)中，RR为已公开文献中的某一化学成分通过某一作用途径治疗复杂性疾病的某一指标的回调率，其中，N、M和D依次为所述指标对应的正常对照组、模型组和给药组的数值；
b)根据回调率RR计算药效得分值ES；
式(2)中，药效得分值ES(a)是指化学成分a通过m条作用途径治疗复杂性疾病的均化回调率，用于指示化学成分a治疗复杂性疾病的作用；RRij是指在已公开文献数据中化学成分a通过作用途径i作用复杂性疾病的回调率；i指治疗复杂性疾病的某一条作用途径，m是指治疗复杂性疾病相关作用途径的数量；j指已公开文献中的某一具体指标，n是指已公开文献中相关指标数据的总数量；
c)根据药效得分值ES计算校正药效得分值AES；
式(3)中，校正药效得分值AES(a)是指中药中的化学成分a治疗复杂性疾病的综合回调率，用于衡量针对复杂性疾病各化学成分在中药中的重要性；c(a)为化学成分a在中药中的含量，w为中药中已定量的化学成分的总数目；
(3)根据校正药效得分值的高低，选择能够体现中药药效的化学成分组合，将其作为中药全方实现药效的潜在效应化学标志物群；
(4)通过验证实验，判断所述潜在效应化学标志物群用于治疗复杂性疾病或作用于疾病相关模型后的相关指标结果与中药全方的指标结果是否存在差异，若差异不显著，则所述潜在效应化学标志物群判定为效应化学标志物群；若差异显著，重复步骤(3)和(4)，调整化学成分组合，直至差异不显著，获得所述效应化学标志物群。
本发明上述方法除适用于中药外，还可用于植物药。
上文所述的潜在效应化学标志物群是指根据校正药效得分值选取的可能代表中药中与全方药效相当的化学成分组合；经过实验验证后，才能确定该潜在效应化学标志物群是否就是效应化学标志物群。
所述的正常对照组是指不给予造模处理的对照；所述模型组是指通过造模处理，得到的疾病相关模型；所述给药组是指对疾病相关模型给予某化学成分处理。
上述提到的已公开文献中对于某化学成分治疗某一复杂性疾病的指标数据一般由多个，在计算药效得分值ES和校正药效得分值AES时，考虑的是所有检索到的相关公开文献中的所有指标数据。
对于大多数中药而言，其发挥治疗作用的药效物质仍然不清。对于这些中药常常是选取其中含量较高或相对容易检测的成分进行质量评价，而这些成分常常与中药的临床药效无关。本发明不仅仅考虑中药中各成分的含量，还考虑了各成分对于疾病治疗各作用途径的作用，能够较全面地辨识出中药发挥治疗作用的效应化学标志物群，为应用效应化学标志物群进行相关中药的质量评价、质量控制、作用机制的进一步研究、以及相关中药的二次开发，中药新药的创制提供基础。
本发明提供了一种具体的中药效应化学标志物群的辨识方法，其中，所述中药为注射用血塞通；所述复杂性疾病为心血管疾病。
注射用血塞通的主要成分为三七总皂苷，针对其中的主要成分，如三七皂苷R1、人参皂苷Rg1、Rb1等，有较多的定性、定量研究；然而，现有的研究较少涉及其中的微量成分。为进一步明确注射用血塞通的化学组成，本发明对该制剂的化学成分进行了系统全面的研究。首先，根据极性不同，通过制备液相色谱将其分为10个组分，以达到富集微量成分的目的；而后将这10个组分分别用液质联用分析，结合相关对照品及文献知识，鉴定或推测其中的成分。
作为优选，步骤(1)中，获取中药中各化学成分种类的方法，包括：
(A)采用液相色谱技术，将所述中药中的化学成分按极性的不同进行分组；
(B)通过液相色谱-质谱技术分别对不同组分进行分析，获得所述中药中各化学成分的种类和含量。
具体地，步骤(A)中，所述液相色谱的条件为：色谱柱为AglientZorbax SB-C18(21.2mm×250mm,7μm)；流动相为水(A)和乙腈(B)；流速为10mL/min；洗脱梯度为：0-30min，19％-21％B；30-40min，21％-28％B；40-55min，28％-33％B；55-85min，33％-45％B；85-95min，45％-70％B；95-105min，70％-95％B；进样量为1mL，检测波长为203nm。
具体地，步骤(B)中，所述液相色谱-质谱的条件为：采自Agilent 1100液相色谱-Finnigan LCQ DecaXPPlus离子阱质谱联用仪；色谱柱为Agilent ZORBAX SB-C18(4.6mm×250mm，5μm)；
质谱仪的采集参数为：负离子模式，离子喷射电压-4.5kV；碰撞气为氦气，鞘气(60)和辅助气(20)为高纯氮；毛细管电压20V；全扫描m/z范围为300-2000。
获取上述化学成分后，尽可能多地测定中药中各化学成分的含量，或者查阅文献，确定其含量。
对于不同的复杂性疾病，可通过疾病的相关研究进展选取药物对复杂性疾病的主要作用途径。作为优选，所述作用途径为心肌保护途径、血管保护途径、抗凝途径、抗高血压途径、抗炎途径、抗氧化途径和改善糖脂代谢途径。上述作用途径能够较全面地反映注射用血塞通对心脑血管疾病的治疗作用。
为了确保能够客观反映中药中各化学成分的回调率，文献的来源以及选取方法非常重要。作为优选，所述文献为数据库Pubmed中以中药中各化学成分名称为关键词检索得到的所有文献。
步骤(3)中，根据校正药效得分值的高低，将其对应的化学成分由高到低进行排序，选择效正药效得分值较高的化学成分且此类化学成分的效正药效得分值的累加值处在50～100％范围内。针对注射用血塞通，本发明选择了人参皂苷Rg1、人参皂苷Rb1、三七皂苷R1、人参皂苷Re和人参皂苷Rd作为潜在效应化学标志物群，上述化学成分的药效得分值分别为45.7％、33.1％、8.7％、4.5％和4.0％；累加值为96.0％。
步骤(4)中，通过验证实验来验证步骤(2)挑选出的化学成分组合是否合理，能够更好地确保辨识的准确性。
当然，验证实验的类型既可以是临床试验，动物实验，也可以是细胞实验，分子生物学实验；只要能够通过与疾病相关的实验指标数据来判断中药全方与潜在效应化学标志物群的药效是否等效即可。
本发明提供的验证实验为大鼠心肌缺血模型实验；对大鼠冠状动脉进行结扎处理，再给结扎处理后大鼠喂注射用血塞通或效应化学标志物群制备的药剂，通过比较两种给药处理后，大鼠的心脏梗死面积、以及乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)，确定两种制剂的药效是否存在差异，来判断潜在效应化学标志物群的准确性。
若选择的潜在效应化学标志物群无法反映全方药效，即：所述潜在效应化学标志物群用于治疗复杂性疾病或作用于疾病相关模型后的相关指标结果与中药全方的指标结果存在差异，则需要，根据校正药效得分值重新选择化学成分。
如选取的校正药效得分值前五的五个成分组合，用于治疗复杂性疾病或作用于疾病相关模型后的相关指标结果与中药全方的指标结果存在差异，则需要选取校正药效得分值前六的六个成分组合，用于治疗复杂性疾病或作用于疾病相关模型后的相关指标结果与中药全方的指标结果进行比较。直至选取的潜在效应化学标志物群用于治疗复杂性疾病或作用于疾病相关模型后的相关指标结果与中药全方的指标结果无差异。
与现有技术相比，本发明具有以下有益效果：
本发明对现有文献的数据进行提取，计算校正药效得分值，选择潜在效应化学标志物群，，并通过实验进行验证，不仅考虑中药中各成分的含量，还考虑了各成分对于疾病治疗各作用途径的作用，能够较全面地辨识出中药中发挥治疗作用的效应化学标志物群，为应用效应化学标志物群进行相关中药的质量评价、质量控制、作用机制的进一步研究以及相关中药的二次开发和中药新药的创制提供了基础。
附图说明
图1为本发明中药的效应化学标志物群的辨识方法的流程示意图；
图2为实施例1中注射用血塞通中主要化学成分的药效得分值ES和校正药效得分值AES；
其中，Ginsenoside Rg1为人参皂苷Rg1，Ginsenoside Rb1为人参皂苷Rb1，Notoginsenoside R1为三七皂苷R1，Ginsenoside Rd为人参皂苷Rd，Ginsenoside Re为人参皂苷Re，Ginsenoside Rh4为人参皂苷Rh4，20(S)-Ginsenoside Rh1为20(S)-人参皂苷Rh1，Notoginsenoside R2为三七皂苷R2，20(S)-Ginsenoside Rg2为20(S)-人参皂苷Rg2，Gypenoside XVII为绞股蓝皂苷XVII，Ginsenoside Rk3为人参皂苷Rk3，Ginsenoside Rg5为人参皂苷Rg5，Ginsenoside Rb2为人参皂苷Rb2，20(R)-Ginsenoside Rh1为20(R)-人参皂苷Rh1，Ginsenoside F1为人参皂苷F1，Ginsenoside F2为人参皂苷F2，Ginsenoside Rk1为人参皂苷Rk1。
图3为实施例1中大鼠心肌缺血模型验证实验中各实验组的药效结果；
其中，A为不同实验组对梗死面积的作用(n＝6)；B为不同实验组对CK活性的作用(n＝10)；C为不同实验组对CK-MB活性的作用(n＝10)；D为不同实验组对LDH活性的作用(n＝10)；
Sham为假手术组；Model为模型组；XSTH为注射用血塞通高剂量组；XSTL为注射用血塞通低剂量组；XST5H为注射用血塞通效应化学标志物群高剂量组；XST5L为注射用血塞通效应化学标志物群低剂量组；
数据用均数±标准差表示，###p<0.001vs.Sham group,*p<0.05vs.Modelgroup,**p<0.01vs.Model group,***p<0.001vs.Model group。
具体实施方式
实施例1
本实施例以中药药剂注射用血塞通为例，辨识治疗心血管疾病的注射用血塞通中能够与全方药效相当的效应化学标志物群。
本实施例中采用的材料与试剂为：乙腈为色谱纯(Merck公司)，去离子水由Milli-Q超纯水系统制备(Millipore公司)。三七皂苷R1、人参皂苷Rg1、Re、Rb1、Rg2、Rh1、Rh1(R)、Rb2、F1、Rd、F2、Rg3、Rg3(R)和七叶胆苷XVII均购自上海融禾医药科技发展有限公司。人参皂苷Rk1、Rg5、F4、Rk3、T5、三七皂苷Rh4、R2(S)、20,22-dehydranotoginsenoside R2由实验室制得。注射用血塞通由黑龙江省珍宝岛制药有限公司提供。其它试剂为分析纯。
具体鉴定方法，如下：
一、获取中药中各化学成分的种类和含量
(1)采用液相色谱技术，将注射用血塞通中的化学成分按极性的不同进行分组。
待测样品的制备：取注射用血塞通约400mg，精密称定，加50％甲醇水溶液溶解，制成100mg/mL浓度的供试品溶液，10000rpm离心10min，取上清液，待用。
仪器及分析方法：采用Agilent 1100型制备液相色谱仪，配G1315B型二极管阵列检测器制备注射用血塞通的不同极性组分。
色谱条件如下：色谱柱为AglientZorbax SB-C18(21.2mm×250mm，7μm)；流动相为水(A)和乙腈(B)；流速为10mL/min。洗脱梯度如下：0-30min，19％-21％B；30-40min，21％-28％B；40-55min，28％-33％B；55-85min，33％-45％B；85-95min，45％-70％B；95-105min，70％-95％B；进样量为1mL，检测波长为203nm。按表1所示，分10段收集流分，分别减压浓缩，用1mL溶剂溶解后离心，取上清液，备用。
表1 注射用血塞通的流分收集与浓缩
(2)通过液相色谱-质谱技术分别对不同组分进行分析，获得注射用血塞通中各化学成分的种类和含量。
各流分通过液质联用分析，结合相关对照品及文献知识进行结构鉴定及推测。多级质谱采自Agilent 1100液相色谱-Finnigan LCQ DecaXPPlus离子阱质谱联用仪。Agilent1100液相色谱仪，配有二元泵、DAD检测器、自动进样器和柱温箱。色谱柱为Agilent ZORBAXSB-C18(4.6mm×250mm，5μm)。洗脱梯度根据各流分进行选择。
Finnigan LCQ DecaXPPlus离子阱质谱仪采集参数：负离子模式，离子喷射电压-4.5kV；碰撞气为氦气，鞘气(60)和辅助气(20)为高纯氮；毛细管电压20V；全扫描m/z范围为300-2000。通过上述方法，注射用血塞通中共有Notoginsenoside H、Majoroside F6、Majoroside F5、2α,3β,12β,20S-tetrahydroxydammar-24-ene-3-O-[β-D-glucopyranosyl(1→4)-β-D-glucopyranosyl]-20-O-[β-D-xyl opyranosyl-(1→6)-β-D-glucopyranoside]、Floralginsenoside P、20-O-Glucoginsenoside Rf、GypenosideLXIX、Notoginsenoside Rw2、Yixinoside A、Gypenoside XLIV、Gypenoside XLIII、Notoginsenoside N、Yesanchinoside E、Vinaginsenoside R11、Floranotoginsenoside A、Gypenoside LVII、Ginsenoside M6-a、Floranotoginsenoside D、Pseudoginsenoside RT2、Majonoside R2、Notoginsenoside M、Notoginsenoside R1、24(S)-PseudoginsenosideF11、Ginsenoside Re3Pseudoginsenoside F11、Gypenoside XLV、Gypenoside LXXII、GinsenosideIa、Notoginsenoside R3、Notoginsenoside K、Quinquenoside IV、Ginsenoside Rg1、Ginsenoside Re、Dihydroxyginsenoside Rb1、Succulentoside D、(20R)-Ginsenoside Rg1、Notoginsenoside Fp1、Gypenoside XLII、Notoginsenoside Rw1、Gypenoside XIX、GinsenosideRf、Chikusetsusaponin L5、Vinaginsenoside R20、Pseudoginsenoside RT3、Gypenoside XLVII、Notoginsenoside B、3β,12β,20S-trihydroxydammar-(E)-24-ene-6-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside、Luperoside G、Ginsenoside F6、Notoginsenoside A、β-D-Glucopyranoside、(3β,12β)-3-[(2-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy]-12-hydroxydammar-24-en-20-ylO-β-D-glucopyranosyl-(1→4)-O-[β-D-xylopyranosyl-(1→6)]-(9CI)、GinsenosideRb1、20(S)-Notoginsenoside R2、Ginsenoside Rg2、20(S)-Ginsenoside Rh1、20(R)-Ginsenoside Rh1、Ginsenoside Rb2、Ginsenoside F1、Ginsenoside Rd、Gypenoside XVII、Notoginsenoside T5、3β,12β-dihydroxydammar-(E)-20(22),24-diene-6-O-β-D-xylopyranosyl-(1→2)-β-D-glucopyranoside、Ginsenoside F4、Ginsenoside F2、Ginsenoside Rk3、Ginsenoside Rh420(S)-Ginsenoside Rg3、20(R)-Ginsenoside Rg3、Ginsenoside Rk1、Ginsenoside Rg5等97个成分被鉴定出来。
采用高效液相色谱法结合相关对照品，测定注射用血塞通中的主要成分含量，结果如下。Ginsenoside Rg1、Ginsenoside Rb1、Notoginsenoside R1、Ginsenoside Re、Ginsenoside Rh4、20(S)-Ginsenoside Rh1、Notoginsenoside R2、20(S)-GinsenosideRg2、Gypenoside XVII、Ginsenoside Rk3、Ginsenoside Rg5、Ginsenoside Rb2、20(R)-Ginsenoside Rh1、Ginsenoside F1、Ginsenoside F2、Ginsenoside Rk1等的含量分别为33.84±0.70、32.03±1.36、9.24±0.30、4.63±0.19、2.45±0.44、1.34±0.14、1.21±0.09、0.88±0.05、0.87±0.07、0.67±0.11、0.60±0.11、0.54±0.05、0.25±0.06、0.22±0.05、0.20±0.02、0.10±0.02％。
上述，Ginsenoside Rg1为人参皂苷Rg1，Ginsenoside Rb1为人参皂苷Rb1，Notoginsenoside R1为三七皂苷R1，Ginsenoside Rd为人参皂苷Rd，Ginsenoside Re为人参皂苷Re，Ginsenoside Rh4为人参皂苷Rh4，20(S)-Ginsenoside Rh1为20(S)-人参皂苷Rh1，Notoginsenoside R2为三七皂苷R2，20(S)-Ginsenoside Rg2为20(S)-人参皂苷Rg2，Gypenoside XVII为绞股蓝皂苷XVII，Ginsenoside Rk3为人参皂苷Rk3，Ginsenoside Rg5为人参皂苷Rg5，Ginsenoside Rb2为人参皂苷Rb2，20(R)-Ginsenoside Rh1为20(R)-人参皂苷Rh1，Ginsenoside F1为人参皂苷F1，Ginsenoside F2为人参皂苷F2，Ginsenoside Rk1为人参皂苷Rk1。
二、根据疾病相关研究进展，选取注射用血塞通治疗心脑血管疾病的主要作用途径，并根据所述作用途径，获取各化学成分在治疗心脑血管疾病中的校正药效得分值
中药常通过多个作用途径整合治疗心脑血管疾病。本实施例中，注射用血塞通治疗心脑血管疾病的作用分为7个方面，包括心肌保护、血管保护、抗凝、抗高血压(文献16-19)、抗炎、抗氧化和改善糖脂代谢。
a)通过在Pubmed上搜寻已公开的文献，得到某一化学成分通过某一作用途径治疗复杂性疾病的某一指标的回调率RR；
RR＝(M-D)/(M-N) (1)；
式(1)中，RR为已公开文献中的某一化学成分通过某一作用途径治疗复杂性疾病的某一指标的回调率，其中，N、M和D依次为所述指标对应的正常对照组、模型组和给药组的数值；
b)根据回调率RR计算药效得分值ES；
式(2)中，药效得分值ES(a)是指化学成分a通过m条作用途径治疗复杂性疾病的均化回调率，用于指示化学成分a治疗复杂性疾病的作用；RRij是指在已公开文献数据中化学成分a通过作用途径i作用复杂性疾病的回调率；i指治疗复杂性疾病的某一条作用途径，m是指治疗复杂性疾病相关作用途径的数量；j指已公开文献中的某一具体指标，n是指已公开文献中相关指标数据的总数量；
c)根据药效得分值ES计算校正药效得分值AES；
式(3)中，校正药效得分值AES(a)是指中药中的化学成分a治疗复杂性疾病的综合回调率，用于衡量针对复杂性疾病各化学成分在中药中的重要性；c(a)为化学成分a在中药中的含量，w为中药中已定量的化学成分的总数目。
根据上述方法，检索Pubmed数据库，得到的注射用血塞通中各成分各回调率(RR)和ES值，如表2所示。
表2 通过检索Pubmed数据库得到的注射用血塞通中各成分各回调率(RR)和ES值
根据上述内容，计算获得上述化学成分的AES数据，结果如图2所示。
三、根据校正药效得分值的高低，选择能够体现中药药效的化学成分组合，将其作为潜在效应化学标志物群
图2中，人参皂苷Rg1、人参皂苷Rb1、三七皂苷R1、人参皂苷Re和人参皂苷Rd的AES分别为45.7％、33.1％、8.7％、4.5％和4.0％，这五个皂苷类成分的累计AES为96.0％。故，将这五个皂苷类成分作为潜在效应化学标志物群进行动物体内的验证实验。
四、通过验证实验，判断所述潜在效应化学标志物群用于治疗心脑血管疾病后的相关指标结果与中药全方的指标结果是否存在差异，若差异不显著，则所述潜在效应化学标志物群判定为能够代替中药全方的效应化学标志物群；若差异显著，重复步骤(3)和(4)，直至差异不显著，获得所述效应化学标志物群
在通过校正药效得分找到注射用血塞通的潜在效应化学标志物群后，潜在效应化学标志物群中各成分按全方中各成分含量混合，并研究其是否在药效学上与全方等效。本实施例中，用于药效学研究的动物模型为经典的大鼠心肌缺血模型。
动物实验过程简述如下：
雄性SD大鼠，230～295g，由北京维通利华实验动物技术有限公司提供。
大鼠腹腔注射12％水合氯醛360mg/kg麻醉后，仰卧位固定。左侧第四肋间隙开胸，以环形钩拉出心脏，在左心耳下方3～4mm处，以6/0无损伤丝线结扎冠状动脉前降支，将心脏放回胸腔，抽空胸腔内空气，关闭胸腔，分别缝合肌层及皮肤，假手术组仅在相应冠脉位置穿线，不结扎。冠脉结扎后15min测定ECG-II，以ST段抬高0.2mV以上者为造型成功。
造型成功的动物及假手术动物共分为6组，每组10只。包括假手术组(Sham)、模型组(Model)、注射用血塞通高剂量组(XSTH)、注射用血塞通低剂量组(XSTL)、注射用血塞通效应化学标志物群高剂量组(XST5H)、注射用血塞通效应化学标志物群低剂量组(XST5L)。
受试药组分别给予血塞通(XST)100mg/kg、150mg/kg，以及血塞通5种主要成分混合物(XST5)100mg/kg、150mg/kg，假手术组和模型对照组给予溶剂。造型后15min开始静脉输注给药，给药体积均为1mL/只，给药时间30min，给药1次。
取血后，经股静脉快速注射1％伊文思蓝1mL/只，随心脏搏动1min后，取下左心脏，用生理盐水冲洗后，-20℃冷冻。心脏均匀切成5片，厚度1～2mm，1％TTC 37℃染色10min，经病理图像分析系统测定梗死区占左心室的百分比。单次给药采用面积法进行计算。给药后24h，腹主动脉取血，低温3000rpm离心10min，取上层血清，Elisa法测定LDH、CK、CK-MB。
各组大鼠心肌缺血损伤后左心室梗死范围的结果见图3A。与假手术组相比，模型组大鼠心肌缺血损伤后左心室梗死范围显著升高。与模型组相比，XSTH、XSTL、XST5H和XST5L均可显著降低大鼠心脏梗死面积，且XST5H与XSTH间，XST5L与XSTL间均无显著性差异。
各组大鼠心肌缺血损伤后心肌酶的活性见图3B、C和D所示。造模后模型组LDH、CK、CK-MB含量均明显升高，与假手术对照组比较有明显差异(p<0.001)，XSTL可显著降低LDH和CK-MB活性，XSTH可显著降低LDH、CK和CK-MB活性；且XST5H与XSTH间，XST5L与XSTL间均无显著性差异。
动物实验结果表明，五个皂苷类成分作为潜在效应化学标志物群与注射用血塞通全方在抗心肌缺血上没有显著差异。该结果验证上述潜在效应化学标志物群判定为能够代替中药全方的效应化学标志物群。
上文步骤(2)中检索的参考文献如下所示：
1王喜军et al.六味地黄丸血中移行成分的分离及结构鉴定.中国天然药物,277-280(2007).
2王喜军,张宁,孙晖,李丽静&吕海涛.六味地黄丸血中移行成分对氢化可的松致大鼠肾虚动物模型的保护作用.中国实验方剂学杂志,33-37(2008).
3王喜军,张宁,孙晖&孙文军.六味地黄丸的血清药物化学研究.中国天然药物,29-32(2004).
4 van Breemen,R.B.,Tao,Y.&Li,W.Cyclooxygenase-2inhibitors in ginger(Zingiber officinale).Fitoterapia 82,38-43(2011).
5 Qi,L.W.et al.Screening and identification of permeable componentsin a combined prescription of Danggui Buxue decoction using a liposomeequilibrium dialysis system followed by HPLC and LC–MS.Journal of separationscience 29,2211-2220(2006).
6 Wang,H.et al.Fractionation and analysis of Artemisia capillarisThunb.by affinity chromatography with human serum albumin as stationaryphase.Journal of Chromatography A 870,501-510(2000).
7赵惠茹,杨广德,贺浪冲&杨银京.用细胞膜色谱法筛选当归中的有效成分.中国药学杂志,13-15(2000).
8陈蓁,王锐平,贺浪冲&徐迪琴.细胞膜色谱法筛选红花中的有效成分.陕西中医,643-644(2004).
9张博&贺浪冲.用细胞膜色谱法分析金刷把中具有细胞毒活性的有效成分.现代医药卫生,2303-2304(2006).
10 Yang,Z.et al.An ultrafiltration high-performance liquidchromatography coupled with diode array detector and mass spectrometryapproach for screening and characterising tyrosinase inhibitors from mulberryleaves.Analytica chimica acta 719,87-95(2012).
11 Tao,Y.,Zhang,Y.,Cheng,Y.&Wang,Y.Rapid screening and identificationofα‐glucosidase inhibitors from mulberry leaves using enzyme‐immobilizedmagnetic beads coupled with HPLC/MS and NMR.Biomedical Chromatography 27,148-155(2013).
12 Tao,Y.,Chen,Z.,Zhang,Y.,Wang,Y.&Cheng,Y.Immobilized magnetic beadsbased multi-target affinity selection coupled with high performance liquidchromatography–mass spectrometry for screening anti-diabetic compounds from aChinese medicine“Tang-Zhi-Qing”.Journal of pharmaceutical and biomedicalanalysis 78,190-201(2013).
13 Tao,Y.,Zhang,Y.,Wang,Y.&Cheng,Y.Hollow fiber based affinityselection combined with high performance liquid chromatography–massspectroscopy for rapid screening lipase inhibitors from lotus leaf.Analyticachimica acta 785,75-81(2013).
14 Xiao,S.,Yu,R.,Ai,N.&Fan,X.Rapid screening natural-origin lipaseinhibitors from hypolipidemic decoctions by ultrafiltration combined withliquid chromatography–mass spectrometry.Journal of pharmaceutical andbiomedical analysis 104,67-74(2015).
15齐炼文et al.基于中医药特点的中药体内外药效物质组生物/化学集成表征新方法.中国药科大学学报,195-202(2010).
16 Ueshima,H.et al.Cardiovascular Disease and Risk Factors in Asia ASelected Review.Circulation 118,2702-2709(2008).
17 Glynn,R.J.&Rosner,B.Comparison of risk factors for the competingrisks of coronary heart disease,stroke,and venous thromboembolism.AmericanJournal of Epidemiology 162,975-982(2005).
18 Shah,A.M.,Banerjee,T.&Mukherjee,D.Coronary,Peripheral andCerebrovascular Disease:a Complex Relationship.Herz 33,475-480(2008).
19 Omar,S.A.&Webb,A.J.Nitrite reduction and cardiovascularprotection.Journal of Molecular and Cellular Cardiology 73,57-69(2014).
20 Guan,L.,Li,W.&Liu,Z.Effect of ginsenoside-Rb1on cardiomyocyteapoptosis after ischemia and reperfusion in rats.Journal of HuazhongUniversity of Science and Technology.Medical sciences＝Hua zhong ke ji da xuexue bao.Yi xue Ying De wen ban＝Huazhong keji daxue xuebao.Yixue Yingdewenban 22,212-215(2002).
21 Wang,Z.,Li,M.,Wu,W.K.,Tan,H.M.&Geng,D.F.GinsenosideRb1preconditioning protects against myocardial infarction after regionalischemia and reperfusion by activation of phosphatidylinositol-3-kinasesignal transduction.Cardiovascular drugs and therapy/sponsored by theInternational Society of Cardiovascular Pharmacotherapy 22,443-452,doi:10.1007/s10557-008-6129-4(2008).
22 Li,G.,Qian,W.&Zhao,C.Analyzing the anti-ischemia-reperfusioninjury effects of ginsenoside Rb1mediated through the inhibition of p38alphaMAPK.Canadian journal of physiology and pharmacology,1-7,doi:10.1139/cjpp-2014-0164(2015).
23 Xia,R.et al.Ginsenoside Rb1preconditioning enhances eNOSexpression and attenuates myocardial ischemia/reperfusion injury in diabeticrats.Journal of biomedicine&biotechnology 2011,767930,doi:10.1155/2011/767930(2011).
24 Yan,X.et al.Ginsenoside rb1protects neonatal rat cardiomyocytesfrom hypoxia/ischemia induced apoptosis and inhibits activation of themitochondrial apoptotic pathway.Evidence-based complementary and alternativemedicine:eCAM 2014,149195,doi:10.1155/2014/149195(2014).
25 Kong,H.L.et al.Anti-hypoxic effect of ginsenoside Rbl on neonatalrat cardiomyocytes is mediated through the specific activation of glucosetransporter-4ex vivo.Acta pharmacologica Sinica 30,396-403,doi:10.1038/aps.2009.2(2009).
26 Wang,X.F.et al.Ginsenoside rb1reduces isoproterenol-inducedcardiomyocytes apoptosis in vitro and in vivo.Evidence-based complementaryand alternative medicine:eCAM 2013,454389,doi:10.1155/2013/454389(2013).
27 Song,Z.et al.Ginsenoside Rb1prevents H2O2-induced HUVEC senescenceby stimulating sirtuin-1pathway.PloS one 9,e112699,doi:10.1371/journal.pone.0112699(2014).
28 Zhou,W.et al.Ginsenoside Rb1blocks homocysteine-inducedendothelial dysfunction in porcine coronary arteries.Journal of vascularsurgery 41,861-868,doi:10.1016/j.jvs.2005.01.054(2005).
29 Lan,T.H.et al.Ginsenoside Rb1prevents homocysteine-inducedendothelial dysfunction via PI3K/Akt activation and PKCinhibition.Biochemical pharmacology 82,148-155,doi:10.1016/j.bcp.2011.04.001(2011).
30 Ohashi,R.et al.Effects of homocysteine and ginsenoside Rb1 onendothelial proliferation and superoxide anion production.The Journal ofsurgical research 133,89-94,doi:10.1016/j.jss.2005.09.016(2006).
31 He,F.,Guo,R.,Wu,S.L.,Sun,M.&Li,M.Protective effects of ginsenosideRb1 on human umbilical vein endothelial cells in vitro.Journal ofcardiovascular pharmacology 50,314-320,doi:10.1097/FJC.0b013e3180cab12e(2007).
32 Li,Q.Y.et al.Ginsenoside Rb1 inhibits proliferation andinflammatory responses in rat aortic smooth muscle cells.Journal ofagricultural and food chemistry 59,6312-6318,doi:10.1021/jf200424k(2011).
33 Lin,X.H.,Hong,H.S.,Zou,G.R.&Chen,L.L.Upregulation of TRPC1/6 maybe involved in arterial remodeling in rat.The Journal of surgical research195,334-343,doi:10.1016/j.jss.2014.12.047(2015).
34 Chai,H.,Wang,Q.,Huang,L.,Xie,T.&Fu,Y.Ginsenoside Rb1 inhibitstumor necrosis factor-alpha-induced vascular cell adhesion molecule-1expression in human endothelial cells.Biological&pharmaceutical bulletin 31,2050-2056(2008).
35 Smolinski,A.T.&Pestka,J.J.Modulation of lipopolysaccharide-inducedproinflammatory cytokine production in vitro and in vivo by the herbalconstituents apigenin(chamomile),ginsenoside Rb(1)(ginseng)and parthenolide(feverfew).Food and chemical toxicology:an international journal publishedfor the British Industrial Biological Research Association 41,1381-1390(2003).
36 Li,X.,Chen,J.X.&Sun,J.J.Protective effects of Panax notoginsengsaponins on experimental myocardial injury induced by ischemia andreperfusion in rat.Zhongguo yao li xue bao＝Acta pharmacologica Sinica 11,26-29(1990).
37 Li,J.et al.The effects of ginsenoside Rb1 on JNK in oxidativeinjury in cardiomyocytes.Archives of pharmacal research 35,1259-1267,doi:10.1007/s12272-012-0717-3(2012).
38 Liu,D.H.et al.Rb1 protects endothelial cells from hydrogenperoxide-induced cell senescence by modulating redox status.Biological&pharmaceutical bulletin 34,1072-1077(2011).
39 Yu,X.et al.Ginsenoside Rb1 ameliorates liver fat accumulation byupregulating perilipin expression in adipose tissue of db/db obesemice.Journal of ginseng research 39,199-205,doi:10.1016/j.jgr.2014.11.004(2015).
40 Yin,H.et al.Ginsenoside-Rg1 enhances angiogenesis and amelioratesventricular remodeling in a rat model of myocardial infarction.Journal ofmolecular medicine 89,363-375,doi:10.1007/s00109-011-0723-9(2011).
41 Wang,X.D.,Gu,T.X.,Shi,E.Y.,Lu,C.M.&Wang,C.Effect and mechanism ofpanaxoside Rg1 on neovascularization in myocardial infarction rats.Chinesejournal of integrative medicine 16,162-166,doi:10.1007/s11655-010-0162-4(2010).
42 Dong,G.et al.Rg1 prevents myocardial hypoxia/reoxygenation injuryby regulating mitochondrial dynamics imbalance via modulation of glutamatedehydrogenase and mitofusin 2.Mitochondrion 26,7-18,doi:10.1016/j.mito.2015.11.003(2015).
43 Zhu,D.et al.Ginsenoside Rg1 protects rat cardiomyocyte fromhypoxia/reoxygenation oxidative injury via antioxidant and intracellularcalcium homeostasis.Journal of cellular biochemistry 108,117-124,doi:10.1002/jcb.22233(2009).
44 Huang,J.et al.Inhibitory Effect of Ginsenoside Rg1 on VascularSmooth Muscle Cell Proliferation Induced by PDGF-BB Is Involved in NitricOxide Formation.Evidence-based complementary and alternative medicine:eCAM2012,314395,doi:10.1155/2012/314395(2012).
45 Gao,Y.et al.Ginsenoside Rg1 inhibits vascular intimal hyperplasiain balloon-injured rat carotid artery by down-regulation of extracellularsignal-regulated kinase 2.Journal of ethnopharmacology 138,472-478,doi:10.1016/j.jep.2011.09.029(2011).
46 Ma,Z.C.et al.Ginsenoside Rg1 inhibits proliferation of vascularsmooth muscle cells stimulated by tumor necrosis factor-alpha.Actapharmacologica Sinica 27,1000-1006,doi:10.1111/j.1745-7254.2006.00331.x(2006).
47 Zhang,H.S.&Wang,S.Q.Ginsenoside Rg1 inhibits tumor necrosisfactor-alpha (TNF-alpha)-induced human arterial smooth muscle cells(HASMCs)proliferation.Journal of cellular biochemistry 98,1471-1481,doi:10.1002/jcb.20799(2006).
48 Zhou,Q.et al.Ginsenoside Rg1 inhibits platelet activation andarterial thrombosis.Thrombosis research 133,57-65,doi:10.1016/j.thromres.2013.10.032(2014).
49 Kimura,Y.,Okuda,H.&Arichi,S.Effects of various ginseng saponins on5-hydroxytryptamine release and aggregation in human platelets.The Journal ofpharmacy and pharmacology 40,838-843(1988).
50 Ma,Z.C.,Gao,Y.,Wang,J.,Zhang,X.M.&Wang,S.Q.Proteomic analysiseffects of ginsenoside Rg1 on human umbilical vein endothelial cellsstimulated by tumor necrosis factor-alpha.Life sciences 79,175-181,doi:10.1016/j.lfs.2005.12.050(2006).
51 Song,Y.et al.Ginsenoside Rg1 exerts synergistic anti-inflammatoryeffects with low doses of glucocorticoids in vitro.Fitoterapia 91,173-179,doi:10.1016/j.fitote.2013.09.001(2013).
52 Wang,Y.et al.Ginsenoside Rg1 regulates innate immune responses inmacrophages through differentially modulating the NF-kappaB and PI3K/Akt/mTORpathways.International immunopharmacology 23,77-84,doi:10.1016/j.intimp.2014.07.028(2014).
53 Du,J.,Cheng,B.,Zhu,X.&Ling,C.Ginsenoside Rg1,a novelglucocorticoid receptor agonist of plant origin,maintains glucocorticoidefficacy with reduced side effects.Journal of immunology 187,942-950,doi:10.4049/jimmunol.1002579(2011).
54 Lee,H.M.,Lee,O.H.,Kim,K.J.&Lee,B.Y.Ginsenoside Rg1 promotesglucose uptake through activated AMPK pathway in insulin-resistant musclecells.Phytotherapy research:PTR 26,1017-1022,doi:10.1002/ptr.3686(2012).
55 Wang,Y.et al.Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3beta signaling and inhibition of themitochondria-dependent apoptotic pathway.PloS one 8,e70956,doi:10.1371/journal.pone.0070956(2013).
56 Zeng,X.,Li,J.&Li,Z.Ginsenoside Rd mitigates myocardial ischemia-reperfusion injury via Nrf2/HO-1 signaling pathway.International journal ofclinical and experimental medicine 8,14497-14504(2015).
57 Cai,B.X.et al.Ginsenoside-Rd,a new voltage-independent Ca2+entryblocker,reverses basilar hypertrophic remodeling in stroke-prone renovascularhypertensive rats.European journal of pharmacology 606,142-149,doi:10.1016/j.ejphar.2009.01.033(2009).
58 Zhang,Y.X.et al.Ginsenoside-Rd exhibits anti-inflammatoryactivities through elevation of antioxidant enzyme activities and inhibitionof JNK and ERK activation in vivo.International immunopharmacology 17,1094-1100(2013).
59 Wang,L.et al.Inhibitory effect of ginsenoside-Rd on carrageenan-induced inflammation in rats.Canadian journal of physiology and pharmacology90,229-236,doi:10.1139/y11-127(2012).
60 Kim,D.H.et al.Ginsenoside Rd inhibits the expressions of iNOS andCOX-2 by suppressing NF-kappaB in LPS-stimulated RAW264.7 cells and mouseliver.Journal of ginseng research 37,54-63,doi:10.5142/jgr.2013.37.54(2013).
61 Li,X.F.,Shi,X.H.&Luo,Q.Z.Protective effect of ginsenoside Re onmyocardial cells of neonatal SD rat subjected to hypoxia injury.Zhonghua shaoshang za zhi＝Zhonghua shaoshang zazhi＝Chinese journal of burns 27,169-172(2011).
62 Xie,J.T.et al.Antioxidant effects of ginsenoside Re incardiomyocytes.European journal of pharmacology 532,201-207,doi:10.1016/j.ejphar.2006.01.001(2006).
63 Chen,C.X.&Zhang,H.Y.Protective effect of ginsenoside Re onisoproterenol-induced triggered ventricular arrhythmia in rabbits.Zhongguodang dai er ke za zhi＝Chinese journal of contemporary pediatrics 11,384-388(2009).
64 Gao,Y.et al.Inhibitory effects of ginsenoside Re on vascularneointimal hyperplasia induced by balloon-injury and ERK signaling inrats.Chinese Pharmaceutical Journal 50,1589-1593,doi:10.11669/cpj.2015.18.003(2015).
65 Yang,B.R.et al.Pro-angiogenic activity of notoginsenoside R1 inhuman umbilical vein endothelial cells in vitro and in a chemical-inducedblood vessel loss model of zebrafish in vivo.Chinese journal of integrativemedicine,doi:10.1007/s11655-014-1954-8(2014).
66 Lee,K.W.,Jung,S.Y.,Choi,S.M.&Yang,E.J.Effects of ginsenoside Re onLPS-induced inflammatory mediators in BV2 microglial cells.BMC complementaryand alternative medicine 12,196,doi:10.1186/1472-6882-12-196(2012).
67 Wu,C.F.et al.Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.Internationalimmunopharmacology 7,313-320,doi:10.1016/j.intimp.2006.04.021(2007).
68 Paul,S.,Shin,H.S.&Kang,S.C.Inhibition of inflammations andmacrophage activation by ginsenoside-Re isolated from Korean ginseng(Panaxginseng C.A.Meyer).Food and chemical toxicology:an international journalpublished for the British Industrial Biological Research Association 50,1354-1361,doi:10.1016/j.fct.2012.02.035(2012).
69 Lee,I.A.,Hyam,S.R.,Jang,S.E.,Han,M.J.&Kim,D.H.Ginsenoside Reameliorates inflammation by inhibiting the binding of lipopolysaccharide toTLR4 on macrophages.Journal of agricultural and food chemistry 60,9595-9602,doi:10.1021/jf301372g(2012).
70 Zhou,X.M.,Cao,Y.L.&Dou,D.Q.Protective effect of ginsenoside-Reagainst cerebral ischemia/reperfusion damage in rats.Biological&pharmaceutical bulletin 29,2502-2505(2006).
71 Chen,L.M.,Zhou,X.M.,Cao,Y.L.&Hu,W.X.Neuroprotection of ginsenosideRe in cerebral ischemia-reperfusion injury in rats.Journal of Asian naturalproducts research 10,439-445,doi:10.1080/10286020801892292(2008).
72 Cho,W.C.et al.Ginsenoside Re of Panax ginseng possessessignificant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.European journal of pharmacology 550,173-179,doi:10.1016/j.ejphar.2006.08.056(2006).
73 Zhang,Z.et al.Ginsenoside Re reduces insulin resistance throughinhibition of c-Jun NH2-terminal kinase and nuclear factor-kappaB.Molecularendocrinology 22,186-195,doi:10.1210/me.2007-0119(2008).
74 Han,D.H.et al.Ginsenoside Re rapidly reverses insulin resistancein muscles of high-fat diet fed rats.Metabolism:clinical and experimental 61,1615-1621,doi:10.1016/j.metabol.2012.04.008(2012).
75 Quan,H.Y.et al.Ginsenoside Re lowers blood glucose and lipidlevels via activation of AMP-activated protein kinase in HepG2 cells andhigh-fat diet fed mice.International journal of molecular medicine 29,73-80,doi:10.3892/ijmm.2011.805(2012).
76 He,K.et al.ROCK-dependent ATP5D modulation contributes to theprotection of notoginsenoside NR1 against ischemia-reperfusion-inducedmyocardial injury.American journal of physiology.Heart and circulatoryphysiology 307,H1764-1776,doi:10.1152/ajpheart.00259.2014(2014).
77 Zhong,L.et al.Estrogen receptor alpha mediates the effects ofnotoginsenoside R1 on endotoxin-induced inflammatory and apoptotic responsesin H9c2 cardiomyocytes.Molecular medicine reports 12,119-126,doi:10.3892/mmr.2015.3394(2015).
78 Zhang,W.J.,Wojta,J.&Binder,B.R.Notoginsenoside R1 counteractsendotoxin-induced activation of endothelial cells in vitro and endotoxin-induced lethality in mice in vivo.Arteriosclerosis,thrombosis,and vascularbiology 17,465-474(1997).
79 Zhang,H.S.&Wang,S.Q.Notoginsenoside R1 from Panax notoginsenginhibits TNF-alpha-induced PAI-1 production in human aortic smooth musclecells.Vascular pharmacology 44,224-230,doi:10.1016/j.vph.2005.12.002(2006).
80 Zhang,H.S.&Wang,S.Q.Notoginsenoside R1 inhibits TNF-alpha-inducedfibronectin production in smooth muscle cells via the ROS/ERK pathway.Freeradical biology&medicine 40,1664-1674,doi:10.1016/j.freeradbiomed.2006.01.003(2006).
81 Yang,Y.et al.Notoginsenoside R1 reduces blood pressure inspontaneously hypertensive rats through a long non-coding RNAAK094457.International journal of clinical and experimental pathology 8,2700-2709(2015).
82 Sun,B.,Xiao,J.,Sun,X.B.&Wu,Y.Notoginsenoside R1 attenuates cardiacdysfunction in endotoxemic mice:an insight into oestrogen receptor activationand PI3K/Akt signalling.British journal of pharmacology 168,1758-1770,doi:10.1111/bph.12063(2013).
83 Jia,C.et al.Notoginsenoside R1 attenuates atherosclerotic lesionsin ApoE deficient mouse model.PloS one 9,e99849,doi:10.1371/journal.pone.0099849(2014).
84 Ahn,S.et al.Anti-inflammatory activity of ginsenosides in LPS-stimulated RAW 264.7cells.Science Bulletin 60,773-784,doi:10.1007/s11434-015-0773-4(2015).
85 Siraj,F.M.,SathishKumar,N.,Kim,Y.J.,Kim,S.Y.&Yang,D.C.GinsenosideF2possesses anti-obesity activity via binding with PPARgamma and inhibitingadipocytedifferentiation in the 3T3-L1 cell line.Journal of enzyme inhibitionand medicinal chemistry 30,9-14,doi:10.3109/14756366.2013.871006(2015).
86 Kim,D.H.et al.The inhibitory effect of ginseng saponins on thestress-induced plasma interleukin-6 level in mice.Neuroscience letters 353,13-16(2003).
87 Huang,Q.et al.Ginsenoside-Rb2 displays anti-osteoporosis effectsthrough reducing oxidative damage and bone-resorbing cytokines duringosteogenesis.Bone 66,306-314,doi:10.1016/j.bone.2014.06.010(2014).
88 Lee,K.T.et al.The antidiabetic effect of ginsenoside Rb2 viaactivation of AMPK.Archives of pharmacal research 34,1201-1208,doi:10.1007/s12272-011-0719-6(2011).
89 Yokozawa,T.,Fujitsuka,N.,Yasui,T.&Oura,H.Effects of ginsenoside-Rb2 on adenine nucleotide content of rat hepatic tissue.The Journal ofpharmacy and pharmacology 43,290-291(1991).
90 Kim,E.J.et al.The ginsenoside-Rb2 lowers cholesterol andtriacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterolor fatty acids conditions.BMB reports 42,194-199(2009).
91 Cho,Y.L.et al.Specific activation of insulin-like growth factor-1receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation.TheJournal of biological chemistry 290,467-477,doi:10.1074/jbc.M114.603142(2015).
92 Chu,S.et al.Ginsenoside Rg5 improves cognitive dysfunction andbeta-amyloid deposition in STZ-induced memory impaired rats via attenuatingneuroinflammatory responses.International immunopharmacology 19,317-326,doi:10.1016/j.intimp.2014.01.018(2014).
93 Kim,T.W.,Joh,E.H.,Kim,B.&Kim,D.H.Ginsenoside Rg5 ameliorates lunginflammation in mice by inhibiting the binding of LPS to toll-like receptor-4on macrophages.International immunopharmacology 12,110-116,doi:10.1016/j.intimp.2011.10.023(2012).
94 Lee,S.M.Anti-inflammatory effects of ginsenosides Rg5,Rz1,and Rk1:inhibition of TNF-alpha-induced NF-kappaB,COX-2,and iNOS transcriptionalexpression.Phytotherapy research:PTR 28,1893-1896,doi:10.1002/ptr.5203(2014).
95 Lee,Y.Y.,Park,J.S.,Jung,J.S.,Kim,D.H.&Kim,H.S.Anti-inflammatoryeffect of ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglialcells.International journal of molecular sciences 14,9820-9833,doi:10.3390/ijms14059820(2013).
96 Kang,K.S.,Kim,H.Y.,Yamabe,N.&Yokozawa,T.Stereospecificity inhydroxyl radical scavenging activities of four ginsenosides produced by heatprocessing.Bioorganic and Medicinal Chemistry Letters 16,5028-5031,doi:10.1016/j.bmcl.2006.07.071(2006).
97 Tian,J.M.et al.Effect of ginsenoside Rg2 on chemical myocardialischemia in rats.Zhongguo Zhong yao za zhi＝Zhongguo zhongyao zazhi＝Chinajournal of Chinese materia medica 28,1191-1192(2003).
98 Cho,Y.S.,Kim,C.H.,Ha,T.S.,Lee,S.J.&Ahn,H.Y.Ginsenoside rg2inhibits lipopolysaccharide-induced adhesion molecule expression in humanumbilical vein endothelial cell.The Korean journal of physiology&pharmacology:official journal of the Korean Physiological Society and theKorean Society of Pharmacology 17,133-137,doi:10.4196/kjpp.2013.17.2.133(2013).
99 Gai,Y.,Ma,Z.,Yu,X.,Qu,S.&Sui,D.Effect of ginsenoside Rh1 onmyocardial injury and heart function in isoproterenol-induced cardiotoxicityin rats.Toxicology mechanisms and methods 22,584-591,doi:10.3109/15376516.2012.702798(2012).
100 Lee,E.S.et al.Ginsenoside metabolite compound K differentiallyantagonizing tumor necrosis factor-alpha-induced monocyte-endothelialtrafficking.Chemico-biological interactions 194,13-22,doi:10.1016/j.cbi.2011.08.008(2011).
101 Jung,J.S.,Kim,D.H.&Kim,H.S.Ginsenoside Rh1 suppresses induciblenitric oxide synthase gene expression in IFN-gamma-stimulated microglia viamodulation of JAK/STAT and ERK signaling pathways.Biochemical and biophysicalresearch communications 397,323-328,doi:10.1016/j.bbrc.2010.05.117(2010).
102 Jung,J.S.et al.Anti-inflammatory mechanism of ginsenoside Rh1 inlipopolysaccharide-stimulated microglia:critical role of the protein kinase Apathway and hemeoxygenase-1 expression.Journal of neurochemistry 115,1668-1680,doi:10.1111/j.1471-4159.2010.07075.x(2010).
103 Gu,W.,Kim,K.A.&Kim,D.H.Ginsenoside Rh1 ameliorates high fat diet-induced obesity in mice by inhibiting adipocyte differentiation.Biological&pharmaceutical bulletin 36,102-107(2013).
104 Le Tran,Q.et al.Triterpene saponins from Vietnamese ginseng(Panaxvietnamensis)and their hepatocytoprotective activity.Journal of naturalproducts 64,456-461,doi:10.1021/np000393f(2001).
105 Maeng,Y.S.et al.Rk1,a ginsenoside,is a new blocker of vascularleakage acting through actin structure remodeling.PloS one 8,e68659,doi:10.1371/journal.pone.0068659(2013).
106 Sun,J.et al.Ginsenoside RK3 Prevents Hypoxia-ReoxygenationInduced Apoptosis in H9c2 Cardiomyocytes via AKT and MAPK Pathway.Evidence-based complementary and alternative medicine:eCAM 2013,690190,doi:10.1155/2013/690190(2013).
107 Cho,K.,Song,S.B.,Tung,N.H.,Kim,K.E.&Kim,Y.H.Inhibition of tnf-α-mediated nf-kb transcriptional activity by dammarane-type ginsenosides fromsteamed flower buds of panax ginseng in hepg2 and sk-hep1 cells.Biomoleculesand Therapeutics 22,55-61,doi:10.4062/biomolther.2013.096(2014).
108 Meng,X.et al.Attenuation of Abeta25-35-induced parallelautophagic and apoptotic cell death by gypenoside XVII through the estrogenreceptor-dependent activation of Nrf2/ARE pathways.Toxicology and appliedpharmacology 279,63-75,doi:10.1016/j.taap.2014.03.026(2014).
109 Meng,X.B.et al.P90RSK and Nrf2 Activation via MEK1/2-ERK1/2Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-InducedApoptotic Death in SH-SY5Y Cells.Evidence-based complementary and alternativemedicine:eCAM 2013,971712,doi:10.1155/2013/971712(2013).
Claims (8)
1.一种中药效应化学标志物群的辨识方法，其特征在于，包括以下步骤：
(1)获取中药中各化学成分的种类和含量；
(2)选取所述中药治疗复杂性疾病的主要作用途径，并根据所述作用途径，获取各化学成分在作用复杂性疾病中的校正药效得分值；
a)从已公开文献的实验数据中，计算得到回调率RR；
RR＝(M-D)/(M-N) (1)；
式(1)中，RR为已公开文献中的某一化学成分通过某一作用途径治疗复杂性疾病的某一指标的回调率，其中，N、M和D依次为所述指标对应的正常对照组、模型组和给药组的数值；
b)根据回调率RR计算药效得分值ES；
式(2)中，药效得分值ES(a)是指化学成分a通过m条作用途径治疗复杂性疾病的均化回调率，用于指示化学成分a治疗复杂性疾病的作用；RRij是指在已公开文献数据中化学成分a通过作用途径i作用复杂性疾病的回调率；i指治疗复杂性疾病的某一条作用途径，m是指治疗复杂性疾病相关作用途径的数量；j指已公开文献中的某一具体指标，n是指已公开文献中某一作用途径相关指标数据的总数量；
c)根据药效得分值ES计算校正药效得分值AES；
式(3)中，校正药效得分值AES(a)是指中药中的化学成分a治疗复杂性疾病的综合回调率，用于衡量针对复杂性疾病各化学成分在中药中的重要性；c(a)为化学成分a在中药中的含量，c(ak)为第k种化学成分在中药中的含量，ES(ak)是指第k种化学成分通过m条作用途径治疗复杂性疾病的均化回调率，w为中药中已定量的化学成分的总数目；
(3)根据校正药效得分值的高低，选择能够体现中药药效的化学成分组合，将其作为中药全方实现药效的潜在效应化学标志物群；
(4)通过验证实验，判断所述潜在效应化学标志物群用于治疗复杂性疾病或作用于疾病相关模型后的相关指标结果与中药全方的指标结果是否存在差异，若差异不显著，则所述潜在效应化学标志物群判定为效应化学标志物群；若差异显著，重复步骤(3)和(4)，调整化学成分组合，直至差异不显著，获得所述效应化学标志物群。
2.如权利要求1所述的辨识方法，其特征在于，所述中药为注射用血塞通；所述复杂性疾病为心血管疾病。
3.如权利要求2所述的辨识方法，其特征在于，步骤(1)中，获取中药中各化学成分的种类的方法，包括：
(A)采用液相色谱技术，将所述中药中的化学成分按极性的不同进行分组；
(B)通过液相色谱-质谱技术分别对不同组分进行分析，获得所述中药中各化学成分的种类和含量。
4.如权利要求3所述的辨识方法，其特征在于，步骤(A)中，所述液相色谱的条件为：色谱柱为AglientZorbax SB-C18，其规格为21.2mm×250mm,7μm；流动相为水A和乙腈B；流速为10mL/min；洗脱梯度为：0-30min，19％-21％B；30-40min，21％-28％B；40-55min，28％-33％B；55-85min，33％-45％B；85-95min，45％-70％B；95-105min，70％-95％B；进样量为1mL，检测波长为203nm。
5.如权利要求3所述的辨识方法，其特征在于，步骤(B)中，所述液相色谱-质谱的条件为：采自Agilent 1100液相色谱-Finnigan LCQ DecaXPPlus离子阱质谱联用仪；色谱柱为Agilent ZORBAX SB-C18，其规格为4.6mm×250mm，5μm。
6.如权利要求2所述的辨识方法，其特征在于，所述作用途径为心肌保护途径、血管保护途径、抗凝途径、抗高血压途径、抗炎途径、抗氧化途径和改善糖脂代谢途径。
7.如权利要求2所述的辨识方法，其特征在于，所述的已公开文献为数据库Pubmed中以中药中各成分化合物名称为关键词检索得到的所有文献。
8.如权利要求2所述的辨识方法，其特征在于，步骤(4)中，所述验证实验为大鼠心肌缺血模型实验。
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278968A (zh) * | 2008-05-26 | 2008-10-08 | 南京海陵中药制药工艺技术研究有限公司 | 具有抗癌辅助作用的复方制剂 |
| CN102100706A (zh) * | 2009-12-18 | 2011-06-22 | 中国科学院大连化学物理研究所 | 一种应用代谢组学对中成药质量评价的方法 |
| CN102183608A (zh) * | 2011-02-27 | 2011-09-14 | 浙江大学 | 一种中药药动学－药效学联合分析方法 |
| CN102879486A (zh) * | 2012-09-05 | 2013-01-16 | 山东大学 | 一种筛选中药药效相关成分的方法及模型建立方法 |
| CN103150490A (zh) * | 2013-02-20 | 2013-06-12 | 浙江大学 | 用于发现中药活性成分及其作用靶点的网络药理学方法 |
| CN104826135A (zh) * | 2014-02-11 | 2015-08-12 | 沈阳药科大学 | 一种在体评价中药药理活性的方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070148268A1 (en) * | 2005-12-23 | 2007-06-28 | Hong Kong Jockey Club Institute Of Chinese Medicine Limted | Chemical compounds and their use as therapeutic agent and means of quality assessment of herbal medicines |
-
2017
- 2017-05-15 CN CN201710339006.5A patent/CN107247867B/zh active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278968A (zh) * | 2008-05-26 | 2008-10-08 | 南京海陵中药制药工艺技术研究有限公司 | 具有抗癌辅助作用的复方制剂 |
| CN102100706A (zh) * | 2009-12-18 | 2011-06-22 | 中国科学院大连化学物理研究所 | 一种应用代谢组学对中成药质量评价的方法 |
| CN102183608A (zh) * | 2011-02-27 | 2011-09-14 | 浙江大学 | 一种中药药动学－药效学联合分析方法 |
| CN102879486A (zh) * | 2012-09-05 | 2013-01-16 | 山东大学 | 一种筛选中药药效相关成分的方法及模型建立方法 |
| CN103150490A (zh) * | 2013-02-20 | 2013-06-12 | 浙江大学 | 用于发现中药活性成分及其作用靶点的网络药理学方法 |
| CN104826135A (zh) * | 2014-02-11 | 2015-08-12 | 沈阳药科大学 | 一种在体评价中药药理活性的方法 |
Non-Patent Citations (3)
| Title |
|---|
| A Network Study of Chinese Medicine Xuesaitong;LinliWang 等;《Evidence-Based Complementary and Alternative Medicine》;20130824;第2013卷;全文 * |
| 基于中医方证代谢组学的生脉散干预老年痴呆症大鼠的药效物质基础研究;卢盛文 等;《世界科学技术-中医药现代化》;20161020;第18卷(第10期);全文 * |
| 抗2型糖尿病中药药效物质发现方法及网络药理学研究;杨振中;《中国博士学位论文全文数据库 医药卫生科技辑》;20160815;第2016年卷(第08期);全文 * |
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