微透析技术结合液质联用的不同黄芪剂量的补阳还五汤在脑缺血损伤大鼠血药动学研究
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摘要
目的:探讨不同黄芪剂量的补阳还五汤益气组与活血组有效成分在MCAO大鼠体内的药动学特征。方法:复制大鼠脑缺血再灌注动物模型,建立补阳还五汤微透析样品的液质联用检测方法,研究补阳还五汤益气组低、中、高剂量(3.09,6.17,12.34 g·kg~(-1)),活血组注射液给药剂量为2.32 g·kg~(-1),股静脉给药后脑缺血再灌注损失大鼠中有效成分的药动学特征。结果:补阳还五汤不同给药组中芒柄花素和芍药苷血液药动学过程符合一房室模型,低剂量益气组和活血组中芒柄花素和芍药苷的半衰期(t_(1/2))分别为(46.89±1.77),(25.47±1.43) min,平均滞留时间(MRT)分别为(67.66±2.55),(36.74±2.07) min,药-时曲线下面积(AUC_(0-t))分别为(39 325.21±7 411.43),(225 496.40±24 990.38) ng·mL~(-1)·min;中剂量益气组和活血组中芒柄花素和芍药苷的t_(1/2)分别为(43.73±0.47),(26.24±1.10) min, MRT分别为(63.09±0.68,37.85±1.59) min,AUC_(0-t)(67 556.41±7 043.40),(242 206.10±19 296.12) ng·mL~(-1)·min;高剂量益气组和活血组中芒柄花素和芍药苷的t_(1/2)分别为(43.34±5.70),(29.37±2.23) min,MRT分别为(62.54±8.22),(42.37±3.22) min,AUC_(0-t)分别为(145 611.50±24 607.85),(259 667.70±27 544.71) ng·mL~(-1)·min。结论:不同黄芪剂量组中芒柄花素的MRT及t_(1/2)均无明显差异。高剂量益气组能延长芍药苷t_(1/2)、MRT,能延缓芍药苷在体内被代谢,有利于芍药苷在体内维持更持久的作用时间。
OBJECTIVE To explore the pharmacokinetics of the active constituents of Buyang Huanwu Yiqi group and Huoxue group in different doses of Astragalus membranaceus in MCAO rats. METHODS The rat model of cerebral ischemia-reperfusion was copied and the liquid-mass spectrometry method of Buyang Huanwu Decoction was established to study the pharmacokinetic characteristics of active ingredients of the MCAO rats after giving low,medium and high doses(3.09,6.17,12.34 g·kg~(-1)) of Yiqi group injection and Huoxue group injection(2.32 g·kg~(-1)). RESULTS The pharmacokinetics of formononetin and paeoniflorin in different administration groups of Buyang Huanwu Decoction accorded with the one-compartment model. The t_(1/2 )of formononetin and paeoniflorin in low-dose Yiqi group and Huoxue group were respectively(46.89±1.77),(25.47±1.43) min,MRT were(67.66±2.55),(36.74±2.07) min,respectively,AUC_(0-t) was(39 325.21±7 411.43),(225 496.40±24 990.38) ng·mL~(-1)·min; medium dose The t_(1/2) of formononetin and paeoniflorin in Yiqi group and Huoxue group were(43.73±0.47),(26.24±1.10) min,respectively,and MRT were(63.09±0.68),(37.85±1.59) min,AUC_(0-t)(67 556.41±7 043.40),(242 206.10±19 296.12) ng·mL~(-1)·min; t_(1/2) of formononetin and paeoniflorin in high-dose Yiqi group and Huoxue group were(43.34±5.70),(29.37±2.23) min,respectively,MRT(62.54±8.22),(42.37±3.22) min,AUC_(0-t) was(145 611.50±24 607.85),(259 667.70±27 544.71) ng·mL~(-1)·min,respectively.CONCLUSION There were no significant differences in MRT and t_(1/2) between formononetin in different doses of jaundice. The high-dose Yiqi group can prolong paeoniflorin t_(1/2) and MRT,which can delay the metabolism of paeoniflorin in the body,which is beneficial to maintain the longer lasting action time of paeoniflorin in the body.
OBJECTIVE To explore the pharmacokinetics of the active constituents of Buyang Huanwu Yiqi group and Huoxue group in different doses of Astragalus membranaceus in MCAO rats. METHODS The rat model of cerebral ischemia-reperfusion was copied and the liquid-mass spectrometry method of Buyang Huanwu Decoction was established to study the pharmacokinetic characteristics of active ingredients of the MCAO rats after giving low,medium and high doses(3.09,6.17,12.34 g·kg~(-1)) of Yiqi group injection and Huoxue group injection(2.32 g·kg~(-1)). RESULTS The pharmacokinetics of formononetin and paeoniflorin in different administration groups of Buyang Huanwu Decoction accorded with the one-compartment model. The t_(1/2 )of formononetin and paeoniflorin in low-dose Yiqi group and Huoxue group were respectively(46.89±1.77),(25.47±1.43) min,MRT were(67.66±2.55),(36.74±2.07) min,respectively,AUC_(0-t) was(39 325.21±7 411.43),(225 496.40±24 990.38) ng·mL~(-1)·min; medium dose The t_(1/2) of formononetin and paeoniflorin in Yiqi group and Huoxue group were(43.73±0.47),(26.24±1.10) min,respectively,and MRT were(63.09±0.68),(37.85±1.59) min,AUC_(0-t)(67 556.41±7 043.40),(242 206.10±19 296.12) ng·mL~(-1)·min; t_(1/2) of formononetin and paeoniflorin in high-dose Yiqi group and Huoxue group were(43.34±5.70),(29.37±2.23) min,respectively,MRT(62.54±8.22),(42.37±3.22) min,AUC_(0-t) was(145 611.50±24 607.85),(259 667.70±27 544.71) ng·mL~(-1)·min,respectively.CONCLUSION There were no significant differences in MRT and t_(1/2) between formononetin in different doses of jaundice. The high-dose Yiqi group can prolong paeoniflorin t_(1/2) and MRT,which can delay the metabolism of paeoniflorin in the body,which is beneficial to maintain the longer lasting action time of paeoniflorin in the body.
引文
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[2] Li YH.Clinical Effects of Buyang Huanwu Decoction Combined with Edaravone Injection in Treating 48 Patients with Acute Ischemic Stroke[J].Chin J Exp Tradit Med Form(中国实验方剂学杂志),2013,19(13):304-307.
[3] Wang JS.Treatment of 68 Cases of Acute and Restorative Period of Ischemic Stroke with Buyang Huanwu Decoction[J].Guangming J Chin Med(光明中医),2014,29(5):998-999.
[4] Han GQ,Wang MG,Chen KM,et al.Protective effect of formononetin on hypoxic injury of cultured osteoblasts in vitro[J].Chin Pharmacol Bull(中国药理学通报),2011,27(5):671-677.
[5] Hu ZY,Xu F,Yan R.Advance in studies on effect of paeoniflorin on nervous system[J].China J Chin Mater Med(中国中药杂志),2013,38(3):297-301.
[6] Rao ML,Tang M,He JY,et al.Effects of paeoniflorin on cerebral blood flow and the balance of PGI2/TXA2 of rats with focal cerebral ischemia-reperfusion injury[J].Acta Pharm Sin(药学学报),2014,49(1):55-60.
[7] Lv L,Zhang HY.A Novel Blood Microdialysis Technique in Freely Moving Rats and Its Application to the Pharmacokinet Study of Danshensu[J].Chin Pharm J(中国药学杂志),2010,45(11):849-852.
[8] Pelkonen O,Kapitulnik J,Gundert-Remy U,et al.Local kinetics and dynamics of xenobiotics[J].Crit Rev Toxicol,2008,38(8):697-720.
[9] Deng YL,Chen DY,Zhou LL.Application of Microdialysis in Study of Targeting Drug Delivery System and Local Pharmacokinetics[J].Chin J Exp Tradit Med Form(中国实验方剂学杂志),2011,17(23):264-268.
[10] Ou Y.Methodology Research for Dynamically Monitoring Alkaloids of Sanmiao Wan in Rat Dialysates Based on Sites-microdialysis[D].Anhui Med Univ(安徽医科大学),2014.
[11] Yan H.Pharmacokinetics of different routes of administration of sinomenine in rabbit blood and joint fluid[D].Central South Univ(中南大学),2014.
[12] Zeng MF,Pan LM,Zhu HX,et al.Comparative pharmacokinetics of baicalin in plasma after oral administration of Huang-Lian-Jie-Du-Tang or pure baicalin in MCAO and sham-operated rats[J].Fitoterapia,2010,81(6):490-496.
[13] Qu Y,Aluisio L,Lord B,et al.Pharmacokinetics and pharmacodynamics of norfluoxetine in rats:Increasing extracellular serotonin level in the frontal cortex[J].Pharmacol,Biochem Be,2009,92(3):469-473.
[14] Bundgaard C,J?rgensen M.An integrated microdialysis rat model for multiple pharmacokinetic/pharmacodynamic investigations of serotonergic agents[J].J Pharmacol Toxicol Methods,2007,55(2):214-223.
[15] Huang JP,Luo Y,Jiang L,et al.Analysis of the current situation of dosage in the study of pharmacokinetics of traditional Chinese medicine[J].Chin Pharma J(中国药学杂志),2012,47(21):1685-1689.
[16] Liao WG,Yu JY,Guo ZL,et al.Microdialysis combined with UPLC-MS/MS method for determination of tetramethylpyrazine and ferulic acid in striatum of awake and anesthetic rats subjected to cerebral ischemia[J].J Pharm Biomed Anal,2016,128:510-518.
[17] Wu YA,Liao FY,Liao WG,et al.Effect of ferulic acid on the brain pharmacokinetics of tetramethylpyrazine in conscious rats[J].Xenobiotica,2017,47(11):973-979.
[18] He FY,Deng KW,Liu WL,et al.Experimental studies on pharmacokinetics of three components in Buyanghuanwu injection on base of total quantum statistical moment[J].China J Chin Mater Med(中国中药杂志),2013,38(2):253-262.
[19] Zhang WX,Chen KQ,Wu JQ.Analysis of 52 cases of drug-induced anaphylactic shock[J].Chin Hosp Pharm J(中国医院药学杂志),2003,23(10):638-643.