基于均匀设计法的附子与甘草配伍减毒研究
|
摘要
目的观察附子、甘草不同配伍比例对附子毒性的影响,探索甘草与附子配伍减毒的最佳比例。方法使用均匀设计表确定附子、甘草的配伍比例;以小鼠死亡率为指标进行附子、甘草不同配伍比例急性毒性评价;多元线性回归分析得到多元函数模型,针对函数模型求偏导数,得到附子、甘草最佳配比;比较附子及最佳配比附子、甘草的急性毒性,验证其减毒效果。结果随着甘草剂量增加,小鼠死亡率整体呈下降趋势。针对多元回归分析得到的多元函数模型求偏导数得附子、甘草最佳配比为0.42∶1。附子半数致死剂量为30.9 g/kg,附子、甘草最佳配比最大耐受量为100 g/kg,小鼠死亡率为20%,附子毒性明显减小。结论附子、甘草配伍比例对附子毒性有一定影响,从整体趋势来看,随着甘草剂量的增加,附子的毒性逐渐越小。
Objective To observe the effects of different compatibility ratios of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma on toxicity of Aconiti Lateralis Radix Praeparata; To explore the best compatibility ratio of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma. Methods The compatibility ratios of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma were confirmed with uniform design method. Based on the mortality rate of mice, the acute toxicity of different compatibility ratios of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma was evaluated; Multiple linear regression analysis was used to obtain multivariate function model. Partial derivative for function model was used to obtain the best compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma; acute toxicity of Aconiti Lateralis Radix Praeparata and best compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma were compared, and its attenuation was verified. Results With the increase of Glycyrrhizae Radix et Rhizoma dosage, the mortality rate of mice was decreasing as a whole. The best ratio of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma obtained through partial derivative of multiple function model was 0.42:1. The lethal dosage of half Aconiti Lateralis Radix Praeparata was 30.9 g/kg. The maximal tolerable dose of best compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma was 100 g/kg. The mortality rate of mice was 20%. The toxicity of Aconiti Lateralis Radix Praeparata decreased significantly. Conclusion The compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma has certain effects on the toxicity of Aconiti Lateralis Radix Praeparata. From the overall trend, as the dosage of Glycyrrhizae Radix et Rhizoma increases, the toxicity of Aconiti Lateralis Radix Praeparata is smaller.
Objective To observe the effects of different compatibility ratios of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma on toxicity of Aconiti Lateralis Radix Praeparata; To explore the best compatibility ratio of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma. Methods The compatibility ratios of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma were confirmed with uniform design method. Based on the mortality rate of mice, the acute toxicity of different compatibility ratios of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma was evaluated; Multiple linear regression analysis was used to obtain multivariate function model. Partial derivative for function model was used to obtain the best compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma; acute toxicity of Aconiti Lateralis Radix Praeparata and best compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma were compared, and its attenuation was verified. Results With the increase of Glycyrrhizae Radix et Rhizoma dosage, the mortality rate of mice was decreasing as a whole. The best ratio of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma obtained through partial derivative of multiple function model was 0.42:1. The lethal dosage of half Aconiti Lateralis Radix Praeparata was 30.9 g/kg. The maximal tolerable dose of best compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma was 100 g/kg. The mortality rate of mice was 20%. The toxicity of Aconiti Lateralis Radix Praeparata decreased significantly. Conclusion The compatibility of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma has certain effects on the toxicity of Aconiti Lateralis Radix Praeparata. From the overall trend, as the dosage of Glycyrrhizae Radix et Rhizoma increases, the toxicity of Aconiti Lateralis Radix Praeparata is smaller.
引文
[1]国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技出版社,2015:191-192.
[2]张金莲,曾昭君,张冰,等.附子临床不良反应分析[J].中国实验方剂学杂志,2014,20(18):228-230.
[3]常吉梅,常娟.附子减毒与药效探析[J].中医学报,2012,27(9):1168-1169.
[4]考玉萍,张化为.大剂量食用附子安全性和有效性研究[J].陕西中医,2013,34(4):478-480.
[5] LI S, LI F, LI Y, et al. A review of traditional and current methods used to potentially reduce[J]. Journal of Ethnopharmacology,2017,207:237-250.
[6] ZHOU G H, TANG L Y, ZHOU X D, et al. A review on phytochemistryand pharmacologicalactivitiesoftheprocessedlateralrootof Aconitum carmichaelii Debeaux[J]. Journal of Ethnopharmacology,2015,160:173-193.
[7]章津铭,傅超美,何宇新,等.附子-甘草配伍前后汤液中沉积物的化学组分对比研究[J].中草药,2013,44(2):165-169.
[8]陈秋薇,章津铭,季宁平,等.附子-甘草药对配伍前后汤液相态对比研究[J].中国实验方剂学杂志,2014,20(2):92-95.
[9]缪萍,裘福荣,曾金,等.甘草诱导CYP3A促进附子代谢的减毒配伍机制[J].中华中医药杂志,2014,29(9):2813-2817.
[10]王芳.附子与干姜、甘草配伍使用后乌头碱含量的变化研究[J].中医临床研究,2014,6(25):22-25.
[11]王云.黑附子及配伍甘草、干姜对小鼠致死毒性随机平行对照研究[J].实用中医内科杂志,2014,29(4):68-70.
[12]李莹,傅超美,彭伟,等.四逆汤中甘草减附子之毒的代谢组学研究[J].中国中药杂志,2016,41(8):1523-1529.
[13]李莹,傅超美,任波,等.基于MI-RI大鼠心肌细胞代谢组学研究四逆汤中附子配伍甘草解毒增效机制[J].中国中药杂志,2014,39(16):3166-3171.
[14]王利勤,张宇燕,何昱,等.附子、甘草有效成分不同配伍比例对H9c2心肌细胞缺氧缺糖损伤的影响[J].中医杂志,2016,57(15):1327-1330.
[15]周天梅,杨洁红,万海同,等.附子甘草主要成分配伍对乌头碱致大鼠传代细胞损伤的保护作用[J].北京中医药大学学报,2014,37(1):22-26.
[16]解素花,张广平,孙桂波,等.附子与甘草不同配伍比例配伍减毒的实验研究[J].中国中药杂志,2012,37(15):2210-2213.
[17]张丹,叶强.附子配伍不同甘草炮制品及其比例的研究[J].中国医院药学杂志,2013,33(11):1102-1104.
[18]王英豪,吴水生,李德森,等.基于均匀设计法的钩吻配伍玉叶金花的毒性作用规律研究[J].中国现代应用药学,2016,33(2):150-154.
[19]章津铭.基于毒(效)组分“体外沉积、体内缓释”环节的附子-甘草配伍减毒作用机制研究[D].成都:成都中医药大学,2012.
[20]张广平,朱丽君,周娟,等.附子配伍甘草对CYP3A4体内活性的影响研究[J].中国中药杂志,2012,37(15):2206-2209.
[2]张金莲,曾昭君,张冰,等.附子临床不良反应分析[J].中国实验方剂学杂志,2014,20(18):228-230.
[3]常吉梅,常娟.附子减毒与药效探析[J].中医学报,2012,27(9):1168-1169.
[4]考玉萍,张化为.大剂量食用附子安全性和有效性研究[J].陕西中医,2013,34(4):478-480.
[5] LI S, LI F, LI Y, et al. A review of traditional and current methods used to potentially reduce[J]. Journal of Ethnopharmacology,2017,207:237-250.
[6] ZHOU G H, TANG L Y, ZHOU X D, et al. A review on phytochemistryand pharmacologicalactivitiesoftheprocessedlateralrootof Aconitum carmichaelii Debeaux[J]. Journal of Ethnopharmacology,2015,160:173-193.
[7]章津铭,傅超美,何宇新,等.附子-甘草配伍前后汤液中沉积物的化学组分对比研究[J].中草药,2013,44(2):165-169.
[8]陈秋薇,章津铭,季宁平,等.附子-甘草药对配伍前后汤液相态对比研究[J].中国实验方剂学杂志,2014,20(2):92-95.
[9]缪萍,裘福荣,曾金,等.甘草诱导CYP3A促进附子代谢的减毒配伍机制[J].中华中医药杂志,2014,29(9):2813-2817.
[10]王芳.附子与干姜、甘草配伍使用后乌头碱含量的变化研究[J].中医临床研究,2014,6(25):22-25.
[11]王云.黑附子及配伍甘草、干姜对小鼠致死毒性随机平行对照研究[J].实用中医内科杂志,2014,29(4):68-70.
[12]李莹,傅超美,彭伟,等.四逆汤中甘草减附子之毒的代谢组学研究[J].中国中药杂志,2016,41(8):1523-1529.
[13]李莹,傅超美,任波,等.基于MI-RI大鼠心肌细胞代谢组学研究四逆汤中附子配伍甘草解毒增效机制[J].中国中药杂志,2014,39(16):3166-3171.
[14]王利勤,张宇燕,何昱,等.附子、甘草有效成分不同配伍比例对H9c2心肌细胞缺氧缺糖损伤的影响[J].中医杂志,2016,57(15):1327-1330.
[15]周天梅,杨洁红,万海同,等.附子甘草主要成分配伍对乌头碱致大鼠传代细胞损伤的保护作用[J].北京中医药大学学报,2014,37(1):22-26.
[16]解素花,张广平,孙桂波,等.附子与甘草不同配伍比例配伍减毒的实验研究[J].中国中药杂志,2012,37(15):2210-2213.
[17]张丹,叶强.附子配伍不同甘草炮制品及其比例的研究[J].中国医院药学杂志,2013,33(11):1102-1104.
[18]王英豪,吴水生,李德森,等.基于均匀设计法的钩吻配伍玉叶金花的毒性作用规律研究[J].中国现代应用药学,2016,33(2):150-154.
[19]章津铭.基于毒(效)组分“体外沉积、体内缓释”环节的附子-甘草配伍减毒作用机制研究[D].成都:成都中医药大学,2012.
[20]张广平,朱丽君,周娟,等.附子配伍甘草对CYP3A4体内活性的影响研究[J].中国中药杂志,2012,37(15):2206-2209.