基于撤药分析法的当归系列药对在新生化颗粒中的作用贡献研究

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[摘要]比較评价新生化颗粒缺失当归系列药对前后对急性血瘀大鼠血液流变学和凝血功能的影响，探讨当归系列药对在新生化颗粒中的活血作用贡献。采用冰水浴和皮下注射盐酸肾上腺素共同复制急性血瘀大鼠模型。根据全血黏度（WBV）、血浆黏度（PV）、血沉（ESR）和红细胞压积（HCT）等指标，观察新生化颗粒缺失当归系列药对前后对急性血瘀大鼠血液流变学的影响；以血小板最大聚集率（ADP）、凝血酶时间（TT）、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、血浆纤维蛋白原含量（FIB）观察新生化颗粒缺失当归系列药对前后对血瘀大鼠的血小板聚集和凝血功能的影响。采用多指标综合指数法和主成分分析法综合评价当归系列药对在新生化颗粒中的活血作用贡献。研究结果显示，与正常组比较，模型组的各血液流变学和凝血功能指标均有统计学差异（P<0.01）；与模型组比较，新生化颗粒缺失当归系列药对前后对急性血瘀大鼠的血液流变学和凝血功能的多个指标皆有一定的改善作用。多指标综合指数法和主成分分析法综合评价得出，新生化颗粒对血瘀大鼠的调节作用优于拆方组和生化汤组；新生化颗粒缺失当归系列药对后，各给药组的活血效应均有一定程度的降低；缺失不同的当归药对后对原方的活血效应影响不同，当归系列药对在新生化颗粒中的活血作用贡献的顺序为：当归-益母草>当归-川芎>当归-红花>当归-炙甘草>当归-桃仁>当归-姜炭。该研究表明，当归系列药对是新生化颗粒的重要组成部分，不同的当归系列药对在新生化颗粒中的活血作用贡献不同；且当归-益母草药对在全方中的活血作用贡献最大，与新生化颗粒的组方结构（重用益母草）以及益母草“活血行滞、祛瘀生新”的功效相一致，该方法为新生化颗粒的临床合理应用提供了科学依据，并为复杂方剂的配伍作用研究提供了一定的方法参考。

[关键词]新生化颗粒； 当归； 药对； 活血化瘀； 多指标综合指数法； 主成分分析； 撤药分析法

[Abstract]Xin-Sheng-Hua granule （XSHG） is a popular remedy commonly used in clinic for the treatment of lochiostasis after delivery. To comparatively investigate the roles of herb pairs containing Angelicae Sinensis Radix （Danggui） upon the formula by evaluating the blood coagulation and hemorheology function in acute blood stasis rats， acute blood stasis rat model was established by ice water bath and subcutaneous injection of adrenaline. And the blood stasis mice were administrated intragastrically with different samples of the formula minus herb pairs containing Danggui and the whole formula （XSHG， SHD， DY， DC， DT， DH， DJ and DZ）. The whole blood viscosity （WBV）， plasma viscosity （PV）， erythrocyte sedimentation rate （ESR） and haematocrit （HCT） were applied to evaluate the effects of the formula minus herb pairs containing Danggui on hemorheology of blood stasis rats. The thrombin time （TT）， activated partial thromboplastin time （APTT）， prothrombin time （PT）， and plasma fibrinogen （FIB） were used to observe the effects of the formula minus herb pairs containing Danggui on blood coagulation function of blood stasis rats. Additionally， the maximum aggregation induced by adenosine diphosphate （ADP） was tested to observe the effect of different samples on platelet aggregation index of blood stasis rats.Afterwards， multi-attribute comprehensive index methods and principal component analysis were both applied to comprehensively assess the total effects of the formula minus herb pairs containing Danggui on promoting blood circulation and dissipating blood stasis. Compared with normal group， the hemorheological parameters and coagulation indexes of model group had statistical differences （P<0.01）. Compared with model group， different samples （XSHG， SHD， DY， DC， DT， DH， DJ and DZ） could improve the blood hemorheology indexes， coagulation parameters and platelet aggregation in acute blood stasis rats. According to multi-attribute comprehensive index methods and the principal component analysis， the effects of promoting blood circulation by removing blood stasis became poor when excluding herb pairs containing Danggui from the formula， the sample DY and DC had the weakest effect of activating blood circulation and dissipating blood stasis， and the effect of sample DY was slightly poorer than DC. The orders of contribution of herb pairs containing Danggui on the formula were Danggui-Yimucao>Danggui-Chuanxiong>Danggui-Honghua>Danggui-Zhigancao>Danggui-Taoren>Danggui-Jiangtan. In conclusion， various herb pairs containing Danggui played different roles on the effects of improving the abnormality of hemorheology and coagulation function. And the herb pairs Danggui-Yimucao were particularly important for the formula， which was consistent with the characteristics of XSHG and the traditional effect of Yimucao. Moreover， it could lay foundation to further reveal the compatibility mechanism of XSHG.