基于含药肠吸收液的麻黄-杏仁药对物质基础与作用机制分析
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摘要
目的:探讨不同配比的麻黄-杏仁药对含药肠吸收液中化学成分含量-效应指标之间的关联性,初步阐明该药对的物质基础及作用机制。方法:选用U6(64)均匀设计表安排药对配比,采用UPLC-Q-TOF-MS/MS分析麻黄-杏仁药对含药肠吸收液中主要差异性成分及其含量;观察含药肠吸收液对大鼠气管环舒张率及组织中白细胞介素-2(IL-2),IL-4,肿瘤坏死因子-α(TNF-α)含量的影响;经多元线性回归分析效应指标与主要成分含量的相关性。结果:通过变量重要性投影值>1.5找出该药对的显著性差异成分为去甲基麻黄碱(X1),伪麻黄碱(X2),甲基麻黄碱(X3),苦杏仁苷(X4);该药对能明显增加气管环的舒张率(Y1),升高组织中IL-2(Y2)含量,降低IL-4(Y3)与TNF-α(Y4)含量;以差异性成分含量为自变量,效应指标为因变量,得回归方程分别为Y1=-4 810.119X1+3 516.816X2-2 663.871X3-81.310X4+33.562(r=0.937),Y2=4 203.354X1-2 567.853X2+1 445.790X3+47.460X4+237.192(r=0.996),Y3=587.549X1-456.975X2+366.365X3+6.239X4+27.519(r=0.951),Y4=-21 958.981X1-35 885.568X2+40 943.441X3+944.167X4+4 465.528(r=0.968)。结论:麻黄-杏仁药对平喘的主要物质基础为去甲基麻黄碱、伪麻黄碱、甲基麻黄碱和苦杏仁苷。其平喘机制与各效应成分双向调节气道舒张与收缩功能,以及改变IL-4,IL-2,TNF-α含量等有关。
Objective: To explore the correlation between the content of chemical components and effect index in the intestinal absorption fluid of Ephedrae Herba-Armeniacae Semen Amarum with different proportions,and clarify the material basis and mechanism of the medicine pair. Method: The U6( 64) uniform design was used to arrange the proportions of this medicine pair,the major differential components in intestinal absorption fluid of this medicine pair and their contents were analyzed by UPLC-Q-TOF-MS/MS. Effect of intestinal absorption fluid containing drug on diastolic rate of tracheal ring in rats and the content of interleukin-2( IL-2),IL-4,tumor necrosis factor-α( TNF-α) in the rat tissue was investigated. The correlation between the effect index and the main component content was analyzed by multiple linear regression. Result: After being analyzed by the least squares regression,the significant difference components found by variable importance in the projection( VIP) > 1. 5 were norephedrine( X1),pseudoephedrine( X2),methyl ephedrine( X3) and amygdalin( X4). The medicine pair can obviously relieve the bronchial ring( Y1),increase content of IL-2( Y2),decrease contents of IL-4( Y3) and TNF-α( Y4) in the tissue. Taking contents of major differential components as independent variables( X),effect index as dependent variables( Y), regression equations were obtained as follows: Y1=-4 810. 119 X1+3 516. 816 X2-2 663. 871 X3-81. 310 X4+ 33. 562( r = 0. 937),Y2= 4 203. 354 X1-2 567. 853 X2+ 1 445. 790 X3+ 47. 460 X4+ 237. 192( r = 0. 996),Y3= 587. 549 X1-456. 975 X2+ 366. 365 X3+ 6. 239 X4+ 27. 519( r =0. 951),Y4=-21 958. 981 X1-35 885. 568 X2+ 40 943. 441 X3+ 944. 167 X4+ 4 465. 528( r = 0. 968).Conclusion: Main material bases of Ephedrae Herba-Armeniacae Semen Amarum on asthma are norephedrine,pseudoephedrine,methyl ephedrine and amygdalin, its antiasthmatic mechanism is related to bidirectional regulating airway function of each effect component,changes in IL-4,IL-2 and TNF-α content and so on.
Objective: To explore the correlation between the content of chemical components and effect index in the intestinal absorption fluid of Ephedrae Herba-Armeniacae Semen Amarum with different proportions,and clarify the material basis and mechanism of the medicine pair. Method: The U6( 64) uniform design was used to arrange the proportions of this medicine pair,the major differential components in intestinal absorption fluid of this medicine pair and their contents were analyzed by UPLC-Q-TOF-MS/MS. Effect of intestinal absorption fluid containing drug on diastolic rate of tracheal ring in rats and the content of interleukin-2( IL-2),IL-4,tumor necrosis factor-α( TNF-α) in the rat tissue was investigated. The correlation between the effect index and the main component content was analyzed by multiple linear regression. Result: After being analyzed by the least squares regression,the significant difference components found by variable importance in the projection( VIP) > 1. 5 were norephedrine( X1),pseudoephedrine( X2),methyl ephedrine( X3) and amygdalin( X4). The medicine pair can obviously relieve the bronchial ring( Y1),increase content of IL-2( Y2),decrease contents of IL-4( Y3) and TNF-α( Y4) in the tissue. Taking contents of major differential components as independent variables( X),effect index as dependent variables( Y), regression equations were obtained as follows: Y1=-4 810. 119 X1+3 516. 816 X2-2 663. 871 X3-81. 310 X4+ 33. 562( r = 0. 937),Y2= 4 203. 354 X1-2 567. 853 X2+ 1 445. 790 X3+ 47. 460 X4+ 237. 192( r = 0. 996),Y3= 587. 549 X1-456. 975 X2+ 366. 365 X3+ 6. 239 X4+ 27. 519( r =0. 951),Y4=-21 958. 981 X1-35 885. 568 X2+ 40 943. 441 X3+ 944. 167 X4+ 4 465. 528( r = 0. 968).Conclusion: Main material bases of Ephedrae Herba-Armeniacae Semen Amarum on asthma are norephedrine,pseudoephedrine,methyl ephedrine and amygdalin, its antiasthmatic mechanism is related to bidirectional regulating airway function of each effect component,changes in IL-4,IL-2 and TNF-α content and so on.
引文
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[12]李文宏,潘琳娜,徐国良,等.复方当归汤含药肠吸收液舒张血管平滑肌的研究[J].中国实验方剂学杂志,2012,18(11):205-208.
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[16]朱慧志,张玉,胡国俊,等.基于中医传承辅助系统分析名老中医胡国俊治疗支气管哮喘用药规律[J].中国实验方剂学杂志,2015,21(5):210-215.
[17]Fischer R,ToméD,Mc Ghee J R,et al.Th1 and Th2cells are required for bith eosinophil and neutroph-ilassociated airway inflammatory responses in mice[J].Biochem Biophys Res Commun,2007,357(1):44-49.
[18]许珂玉,王艳杰,赵丹玉,等.补脾益气方药对哮喘大鼠Th1/Th2失衡的调节及机制[J].山东医药,2012,52(20):16-18.
[19]黄伟强,李惠,袁梅,等.支气管哮喘患者外周血T细胞亚群Th1,Th2及其相关细胞因子水平变化及意义[J].山东医药,2015,55(20):40-41.
[20]龚臣,邓静敏.Th17/Treg在支气管哮喘发病机制中的作用及研究进展[J].国际呼吸杂志,2013,7(9):201-205.
[21]Ryan J J,Mcreynolds L J,Keegan A,et al.Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor[J].Immunity,1996,4(2):123-132.
[2]张欢,范欣生,王崇骏,等.古今哮喘方用药规律对比的关联规则研究[J].中国中医药信息杂志,2009,16(3):94-96.
[3]周玲,吴德康,唐于平,等.麻黄中化学成分研究进展[J].南京中医药大学学报,2008,24(1):71-72.
[4]谭镇岳.麻黄、杏仁配伍对苦杏仁毒性影响及最佳比例研究[J].社区医学杂志,2011,9(24):77-78.
[5]谭晓梅,郭阳,余林中,等.麻黄-杏仁药对配伍及不同配比对急性毒性及平喘作用的影响[J].中药药理与临床,2013,29(1):82-84.
[6]谢颖,汤庆发,徐文杰,等.不同配伍比例对麻黄-杏仁药对有效成分含量的影响[J].时珍国医国药,2012,23(11):2686-2688.
[7]宋帅,梁德东,任孟月,等.麻黄-杏仁药对有效成分在大鼠体内组织分布的定量分析[J].中国实验方剂学杂志,2016,22(12):92-97.
[8]谢晶,张丽,曾金祥,等.基于UPLC-Q-TOF-MS/MS技术的短管兔耳草化学成分快速识别研究[J].中国中药杂志,2017,42(11):2123-2130.
[9]刘梦娇,王云,李玲云,等.三黄片化学成分的UPLCQ-TOF-MS/MS快速鉴定分析[J].中国中药杂志,2017,42(9):1685-1692.
[10]杨丽,李莹,王清娴,等.麻黄-杏仁药对配比与有效成分含量变化规律研究[J].中国当代医药,2017,24(5):4-7.
[11]李文宏,徐国良,彭彩霞,等.基于含药肠吸收液法的复方丹参片对大鼠离体胸主动脉环的作用及机制初步研究[J].时珍国医国药,2014,25(3):570-573.
[12]李文宏,潘琳娜,徐国良,等.复方当归汤含药肠吸收液舒张血管平滑肌的研究[J].中国实验方剂学杂志,2012,18(11):205-208.
[13]Trygg J,Holmes E,Lundstedt T.Chemometrics in metabonomics[J].J Proteome Res,2007,6(2):469-479.
[14]李熙民,陆婉琴,秦芝玲,等.苦杏仁甙药物动力学及其毒理初步研究[J].中国新药与临床杂志,1986,5(3):141-143.
[15]刘赜,石倩,杨洋,等.麻黄碱与伪麻黄碱平喘效果及机制比较研究[J].中草药,2009,40(5):771-774.
[16]朱慧志,张玉,胡国俊,等.基于中医传承辅助系统分析名老中医胡国俊治疗支气管哮喘用药规律[J].中国实验方剂学杂志,2015,21(5):210-215.
[17]Fischer R,ToméD,Mc Ghee J R,et al.Th1 and Th2cells are required for bith eosinophil and neutroph-ilassociated airway inflammatory responses in mice[J].Biochem Biophys Res Commun,2007,357(1):44-49.
[18]许珂玉,王艳杰,赵丹玉,等.补脾益气方药对哮喘大鼠Th1/Th2失衡的调节及机制[J].山东医药,2012,52(20):16-18.
[19]黄伟强,李惠,袁梅,等.支气管哮喘患者外周血T细胞亚群Th1,Th2及其相关细胞因子水平变化及意义[J].山东医药,2015,55(20):40-41.
[20]龚臣,邓静敏.Th17/Treg在支气管哮喘发病机制中的作用及研究进展[J].国际呼吸杂志,2013,7(9):201-205.
[21]Ryan J J,Mcreynolds L J,Keegan A,et al.Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor[J].Immunity,1996,4(2):123-132.