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蒙药“诃子解草乌毒”的配伍比例研究
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| 篇名： | 蒙药“诃子解草乌毒”的配伍比例研究 |
| TITLE： | |
| 摘要： | 目的：探讨蒙药“诃子解草乌毒”的最佳配伍比例。方法：将40只大鼠随机分为空白对照组（0.05％羧甲基纤维素钠溶液）、生草乌组（以生药量计0.12 g/kg）和生草乌-诃子（1 ∶ 3、1 ∶ 1、3 ∶ 1，质量比）组（生草乌给药量以生药计均为0.12 g/kg），每组8只；每天灌胃给药1次，连续给药28 d；末次给药0.5 h后，测定大鼠血清中肌钙蛋白（cTn-I）、肌红蛋白（MB）含量，并观察其心脏病理结构变化，以考察诃子对草乌致心脏毒性的解毒作用。采用平衡透析法并联合液质联用技术测定草乌中3种乌头碱（乌头碱、新乌头碱和次乌头碱，质量浓度均为5、10、20、40、80、160、400 ng/mL）与正常人血浆的血浆蛋白结合率；然后固定3种乌头碱的质量浓度均为100 ng/mL，考察加入不同比例诃子中主要解毒成分单宁酸后（3种乌头碱与诃子的质量比均分别为1 ∶ 0.025、1 ∶ 0.075、1 ∶ 0.1、1 ∶ 0.5），对3种乌头碱血浆蛋白结合率的影响，以考察诃子解草乌致心脏毒性的可能机制。结果：在解毒实验中，与空白对照组比较，生草乌组大鼠血清中cTn-I、MB含量显著升高（P＜0.05），心肌组织出现细胞排列紊乱、细胞固缩、胞浆炎染等明显病理结构改变。与生草乌组比较，生草乌-诃子（1 ∶ 3、1 ∶ 1、3 ∶ 1）组大鼠血清中cTn-I、MB含量均显著降低（P＜0.05），并且生草乌-诃子（3 ∶ 1、1 ∶ 1）组含量与空白对照组差异无统计学意义（P＞0.05）；心肌组织病变都得到不同程度改善，其中生草乌-诃子（3 ∶ 1）组大鼠心肌组织结构与空白对照组相似。在机制考察试验中，在不同质量浓度下，草乌中3种乌头碱与正常人血浆的血浆蛋白结合率均约为30％，差异均无统计学意义（P＞0.05），且无明显的浓度依赖性；加入单宁酸后草乌中3种乌头碱的血浆蛋白结合率均不同程度降低，当3种乌头碱与单宁酸按1 ∶ 0.1、1 ∶ 0.075、1 ∶ 0.5比例配伍时，血浆蛋白结合率显著降低（P＜0.05），且有配伍比例的依赖性。结论：生草乌-诃子（3 ∶ 1）配伍使用对草乌致心脏毒性的解毒效果最好；在此配伍比例下，草乌中3种乌头碱与正常人血浆的血浆蛋白结合率相对较高，游离药物浓度相对较低。 |
| ABSTRACT： | OBJECTIVE： To investigate the best compatibility proportion of Mongolian medicine “Terminalia chebula decomposing the poison of Aconitum kusnezoffii”. METHODS： Totally 40 rats were randomly divided into blank control group （0.05％ CMC-Na）， raw A. kusnezoffii group （0.12 g/kg by crude drug） and raw A. kusnezoffii-T. chebula （1 ∶ 3，1 ∶ 1，3 ∶ 1， mass ratio） group （0.12 g/kg raw A. kusnezoffii by raw material）， 8 rats in each group. They were given relevant medicine intragastrically once a day， for consecutive 28 d. 0.5 h after last medication， serum contents of cTn-I and MB were determined， and the changes of cardiological structure were observed； the detoxification effects of T. chebula on cardiotoxicity induced by A. kusnezoffii were investigated. Binding rates of 3 kinds of aconitine （concentrations of aconitine， mesaconitine and hypaconitine were 5， 10， 20， 40， 80， 160， 400 ng/mL） to binding rate of plasma protein with normal human plasma were determined by equilibrium dialysis combined with liquid chromtography-mass spectrometry. The concentrations of 3 kinds of aconitine were fixed as 100 ng/mL. After adding main detoxification component tannic acid in different proportions of T. chebula （1 ∶ 0.025， 1 ∶ 0.075， 1 ∶ 0.1， 1 ∶ 0.5）， the effects of them on plasma protein binding rate of 3 kinds of aconitine were investigated； the possible mechanism of T. chebula decomposing the poison of A. kusnezoffii inducing cardiotoxicity were investigated. RESULTS： In detoxification experiment， compared with blank control group， serum contents of cTn-I and MB were increased significantly in raw A. kusnezoffii group （P＜0.05）. There were obvious pathological changes in myocardial tissue， such as disorder of cell arrangement， cell shrinkage and cytoplasm staining. Compared with raw A. kusnezoffii group， serum contents of cTn-I and MB in raw A. kusnezoffii-T. chebula （1 ∶ 3， 1 ∶ 1， 3 ∶ 1） groups were decreased significantly （P＜0.05）， and there was no significant difference between the raw A. kusnezoffii-T. chebula （3 ∶ 1， 1 ∶ 1） groups and blank control group （P＞0.05）； myocardial pathological changes were improved to varying degrees. The structure of myocardial tissue in raw A. kusnezoffii-T. chebula （3 ∶ 1） groups were similar to blank control group. In the mechanism investigation experiment under the condition of different concentrations， plasma protein binding rates of 3 kinds of aconitine with normal human plasma were about 30％， without statistical significance （P＞0.05） and significant concentration-dependent manner. After adding tannic acid， plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii was decreased to different extent； when 3 kinds of aconitine were combined with tannic acid in the ratio of 1 ∶ 0.1， 1 ∶ 0.075 and 1 ∶ 0.5， the plasma protein binding rate decreased significantly （P＜0.05）， in proportion-dependent manner. CONCLUSIONS： Compatible use of raw A. kusnezoffii-T. chebula （3 ∶ 1） show that best detoxification effect on A. kusnezoffii-induced cardiotoxicity. Under this compatibility ratio， the plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii with normal human plasma is relatively high and the free drug concentration is relatively low. |
| 期刊： | 2019年第30卷第11期 |
| 作者： | 刘爽，张晓菲，苗鑫，邢海燕，李刚 |
| AUTHORS： | LIU Shuang，ZHANG Xiaofei，MIAO Xin，XING Haiyan，LI Gang |
| 关键字： | 草乌；诃子；心脏毒性；解毒作用；血浆蛋白结合率；配伍比例 |
| KEYWORDS： | Aconitum kusnezoffii；Terminalia chebula；Cardiotoxicity； Detoxification； Plasma protein binding rate； Compatibility proportion |
| 阅读数： | 614 次 |
| 本月下载数： | 6 次 |
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