草乌与(生、法)半夏配伍3个毒性成分毒代动力学变化研究
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摘要
目的:探讨草乌与(生、法)半夏配伍毒代动力学变化。方法:采用雄性SD大鼠48只,随机分为草乌醇提组、草乌与法半夏醇提组、草乌与生半夏醇提组、草乌水提组、草乌与法半夏水提组、草乌与生半夏水提组,分别单次以《中华人民共和国药典》(2015版)中草乌最大剂量给药(0. 06g/kg),设给药前和给药后共13个采血时间点,采用LC-MS/MS检测血浆样品,血药浓度-时间数据经DAS2. 0软件处理计算毒代动力学参数。结果:3个毒性成分的AUC(0-t)变化:乌头碱:与单用醇提草乌相比,醇提草乌与法半夏配伍明显降低;与单用水提草乌相比,与生半夏配伍后增大明显。新乌头碱:与单用醇提草乌相比,在醇提草乌与法半夏配伍明显降低,但与生半夏配伍明显增大;与单用水提草乌相比,水提草乌与生半夏配伍明显增加。次乌头碱:与单用醇提草乌相比,在醇提草乌与法半夏配伍明显降低,水提物的变化与醇提一致。Cmax变化:乌头碱:与单用水提草乌相比,水提草乌与生半夏配伍后显示增大。新乌头碱:与单用醇提草乌相比,醇提草乌与法半夏配伍降低,但与生半夏配伍后增大;与单用水提草乌相比,水提草乌与生半夏配伍后明显增加。次乌头碱:与单用醇提草乌相比,在醇提草乌与法半夏配伍后明显降低。结论:总体可见生半夏可使草乌中双酯型生物碱的吸收程度与速率增加;法半夏可使草乌中双酯型生物碱的吸收程度与速率减小。
Objective: To investigate the toxicokinetics change in the compatibility of aconite kusnezoffii radix(CW) and pinelliae rhizoma(SBX,FBX). Method: Forty-eight SD rats were random divided into six groups : the alcohol extraction of CW,the alcohol extraction of CW compatible with FBX,the alcohol extraction of CW compatible with SBX,the water extraction of CW,the water extraction of CW compatible with FBX,the water extraction of CW compatible with SBX. Administration to rats of each group one time on the biggest dose of CW in Pharmacopoeia of People's Republic of China(2015 edition),plasma samples of thirteen points were got before and after administration,which were detected the content of aconitine,mesaconitine and hypaconitine by LC-MS/MS. Then the data of drug concentration-time were treated by DAS 2. 0 software and calculated the parameters of toxicokinetics. Results: Compared with alcohol extract of CW,the AUC(0-t)and Cmax of aconitine,mesaconitine and hypaconitine were all increased in the alcohol extraction of CW compatible with SBX,but they were all reduced in the alcohol extraction of CW compatible with FBX. Compared with water extract of CW,the AUC(0-t)faconitine,mesaconitine and hypaconitine were basically unchanged,while the Cmax of aconitine and mesaconitine were increased sharply in the water extraction of CW compatible with SBX; the AUC(0-t)of aconitine was decrease,mesaconitine's basically constant but hypaconitine's became larger,the Cmax of them all basically unchanged. Conclusion: SBX could increase the absorption and rate of Diester alkaloid in CW,but FBX could reduce them.
Objective: To investigate the toxicokinetics change in the compatibility of aconite kusnezoffii radix(CW) and pinelliae rhizoma(SBX,FBX). Method: Forty-eight SD rats were random divided into six groups : the alcohol extraction of CW,the alcohol extraction of CW compatible with FBX,the alcohol extraction of CW compatible with SBX,the water extraction of CW,the water extraction of CW compatible with FBX,the water extraction of CW compatible with SBX. Administration to rats of each group one time on the biggest dose of CW in Pharmacopoeia of People's Republic of China(2015 edition),plasma samples of thirteen points were got before and after administration,which were detected the content of aconitine,mesaconitine and hypaconitine by LC-MS/MS. Then the data of drug concentration-time were treated by DAS 2. 0 software and calculated the parameters of toxicokinetics. Results: Compared with alcohol extract of CW,the AUC(0-t)and Cmax of aconitine,mesaconitine and hypaconitine were all increased in the alcohol extraction of CW compatible with SBX,but they were all reduced in the alcohol extraction of CW compatible with FBX. Compared with water extract of CW,the AUC(0-t)faconitine,mesaconitine and hypaconitine were basically unchanged,while the Cmax of aconitine and mesaconitine were increased sharply in the water extraction of CW compatible with SBX; the AUC(0-t)of aconitine was decrease,mesaconitine's basically constant but hypaconitine's became larger,the Cmax of them all basically unchanged. Conclusion: SBX could increase the absorption and rate of Diester alkaloid in CW,but FBX could reduce them.
引文
1马天宇,俞腾飞,李树民.乌头类中药毒代动力学及代谢组学研究进展.中国中药杂志,2014; 39(11)∶1972~1975
2 陈馥馨. 782个含十八反、十九畏内服成药方组成与主治分析.中国医药学报,1987; 2(2)∶26~29
3 赵华,李新莉.半夏与乌头配伍对小鼠毒性作用的实验研究.长春中医药大学学报,2012; 28(1)∶17~18
4 张作舟,刘启旺,朱怀宁,等.中药十八反配伍实验研究-乌头反半夏急性毒性实验小结.中药通报,1983; 8(4)∶31~34
5 高晓山,陈馥馨.近年来中药十八反十九畏药理研究的进展与展望.黑龙江中医药,1986;(2)∶52~55
6 李居林.中药"十八反"动物实验报告.长春中医学院学报,1988; 2(3)∶89~89
7 孙世晓,许蔚,王凤,等.生附子、生半夏配伍后急性毒性的实验研究.中医药信息,2011; 28(2)∶104~106
8 刘文龙,宋凤瑞,刘志强,等.川乌与半夏配伍禁忌的化学研究.化学通报,2008; 71(6)∶435~438
9 李玲,马瑜红,欧阳静萍.附子配伍半夏对大鼠影响的实验研究.中国现代药物应用,2009; 3(5)∶5~6
10 刘刚.川乌配法半夏对大鼠的长期毒性观察.中国民族民间医药,2012; 19(20)∶42~43
11 凌一揆,罗光宇,李玉纯,等.制川乌反法半夏的初步试验——中药"十八反"相互作用的研究之一.成都中医学院学报,1987; 10(2)∶32~36
12沈红,朱玲英,姚楠,等.甘草与附子配伍对乌头碱、新乌头碱、次乌头碱大鼠药动学的影响.中药材,2011; 34(6)∶937~942
13 章津铭,傅超美,秦素红,等. LC-MS/MS比较研究附子配伍甘草对大鼠体内次乌头碱药动学影响.世界科学技术-中医药现代化,2011; 13(6)∶1048~1052
14 王志琪,曾嵘,谭志荣,等.附子与甘草配伍前后乌头碱和甘草次酸在大鼠体内的药动学比较.中成药,2012; 34(12)∶2305~2309
15 Csupor D,Forgo PWenzig E M,Bauer R,et al. Bisnorditerpene,norditerpene and lipo-alkaloids from Aconitum toxicum. Journal of Natural Products,2008; 71(10)∶1779~1782
16 张亚囡,黄幼异,鲍志烨.半夏酸水渗漉液单次给药对小鼠肝毒性"量-时-毒"关系研究.中国药物警戒,2011; 8(1)∶15~19
17 杨守业,叶文华,吴子伦,等.半夏炮制前后对小白鼠急性、亚急性和蓄积性毒性的研究.中成药,1988;(7)∶18~19
18 Zhang Z H,Zhao Y Y,Cheng X L,et al. General toxicity of Pinellia ternata(Thunb.)Berit. in rat∶a metabonomic method for profiling of serum metabolic changes. Journal of Ethnopharmacology,2013; 149(1)∶303~310
19 Shin S,Park D,Jeon J H,et al. Effect of Pinellia ternata,extract on fetal development of rats. Reproductive Toxicology,2007; 24(1)∶74~74
20 王超,王宇光,梁乾德,等. UPLC/Q-TOFMS分析十八反乌头半夏配伍化学成分的变化.药学学报,2010; 45(10)∶1301~1306
21 张鲁,李遇伯,李利新,等.制川乌与法半夏不同比例配伍组合对乌头类生物碱的影响.中草药,2013; 44(6)∶681~685
2 陈馥馨. 782个含十八反、十九畏内服成药方组成与主治分析.中国医药学报,1987; 2(2)∶26~29
3 赵华,李新莉.半夏与乌头配伍对小鼠毒性作用的实验研究.长春中医药大学学报,2012; 28(1)∶17~18
4 张作舟,刘启旺,朱怀宁,等.中药十八反配伍实验研究-乌头反半夏急性毒性实验小结.中药通报,1983; 8(4)∶31~34
5 高晓山,陈馥馨.近年来中药十八反十九畏药理研究的进展与展望.黑龙江中医药,1986;(2)∶52~55
6 李居林.中药"十八反"动物实验报告.长春中医学院学报,1988; 2(3)∶89~89
7 孙世晓,许蔚,王凤,等.生附子、生半夏配伍后急性毒性的实验研究.中医药信息,2011; 28(2)∶104~106
8 刘文龙,宋凤瑞,刘志强,等.川乌与半夏配伍禁忌的化学研究.化学通报,2008; 71(6)∶435~438
9 李玲,马瑜红,欧阳静萍.附子配伍半夏对大鼠影响的实验研究.中国现代药物应用,2009; 3(5)∶5~6
10 刘刚.川乌配法半夏对大鼠的长期毒性观察.中国民族民间医药,2012; 19(20)∶42~43
11 凌一揆,罗光宇,李玉纯,等.制川乌反法半夏的初步试验——中药"十八反"相互作用的研究之一.成都中医学院学报,1987; 10(2)∶32~36
12沈红,朱玲英,姚楠,等.甘草与附子配伍对乌头碱、新乌头碱、次乌头碱大鼠药动学的影响.中药材,2011; 34(6)∶937~942
13 章津铭,傅超美,秦素红,等. LC-MS/MS比较研究附子配伍甘草对大鼠体内次乌头碱药动学影响.世界科学技术-中医药现代化,2011; 13(6)∶1048~1052
14 王志琪,曾嵘,谭志荣,等.附子与甘草配伍前后乌头碱和甘草次酸在大鼠体内的药动学比较.中成药,2012; 34(12)∶2305~2309
15 Csupor D,Forgo PWenzig E M,Bauer R,et al. Bisnorditerpene,norditerpene and lipo-alkaloids from Aconitum toxicum. Journal of Natural Products,2008; 71(10)∶1779~1782
16 张亚囡,黄幼异,鲍志烨.半夏酸水渗漉液单次给药对小鼠肝毒性"量-时-毒"关系研究.中国药物警戒,2011; 8(1)∶15~19
17 杨守业,叶文华,吴子伦,等.半夏炮制前后对小白鼠急性、亚急性和蓄积性毒性的研究.中成药,1988;(7)∶18~19
18 Zhang Z H,Zhao Y Y,Cheng X L,et al. General toxicity of Pinellia ternata(Thunb.)Berit. in rat∶a metabonomic method for profiling of serum metabolic changes. Journal of Ethnopharmacology,2013; 149(1)∶303~310
19 Shin S,Park D,Jeon J H,et al. Effect of Pinellia ternata,extract on fetal development of rats. Reproductive Toxicology,2007; 24(1)∶74~74
20 王超,王宇光,梁乾德,等. UPLC/Q-TOFMS分析十八反乌头半夏配伍化学成分的变化.药学学报,2010; 45(10)∶1301~1306
21 张鲁,李遇伯,李利新,等.制川乌与法半夏不同比例配伍组合对乌头类生物碱的影响.中草药,2013; 44(6)∶681~685