甘草对大鼠体内雷公藤甲素和雷公藤内酯酮代谢物水平的影响  

Effects of Glycyrrhiza uralensis on Metabolites Levels of Triptolide and Triptonide in Rats

作　　者：刘建群[1] 张国华[1] 余昭芬[1] 王雪梅[1] 

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,南昌330004

出　　处：《中国药房》2016年第28期3914-3917,共4页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81160541);江西省卫生厅中医药科研计划项目(No.2011A143)

摘　　要：目的:研究甘草对大鼠体内雷公藤甲素(TPL)和雷公藤内酯酮(TPN)内源代谢物水平的影响。方法:取160只大鼠ig甘草[30 g(生药)/kg]2 h后ip TPN(2.8 mg/kg),连续30 d,收集24 h尿液,合并30 d尿液,采用柱色谱技术和波谱技术分离鉴定其内源代谢物;并采用超高效液相色谱-高分辨飞行时间质谱联用法(UPLC-Q-TOF/MS)确定TPL给药后是否具有共同代谢物。将60只大鼠随机分为TPL空白组、TPL组、甘草+TPL组、TPN空白组、TPN组、甘草+TPN组,各给药组大鼠给药方式及剂量同上,TPL空白组和TPN空白组大鼠分别ip相应溶剂,每天1次,连续7 d;采用UPLC-Q-TOF/MS法研究甘草对大鼠体内TPL、TPN内源代谢物水平的影响。结果:从TPN给药大鼠尿液中共分离出5个内源代谢物,分别鉴定为1-甲基海因、4-氨基烟酸甲酯、3,4-二氢-6-羟基-2-喹啉酮、2,6-二羟基喹啉、2-喹啉酮;TPL给药后大鼠尿液中同样存在这5种代谢物。TPL组大鼠尿液中1-甲基海因水平较TPL空白组显著升高(P<0.05),TPN组大鼠尿液中2,6-二羟基喹啉水平较TPN空白组显著升高(P<0.05);TPL或TPN联合甘草用药后血清中1-甲基海因、2,6-二羟基喹啉水平均降低,较其空白组差异无统计学意义(P>0.05)。结论:本实验首次从TPL和TPN给药大鼠尿液中分离鉴定出了5个内源代谢物;甘草能回调TPL给药大鼠尿液中1-甲基海因水平以及TPN给药后大鼠尿液中2,6-二羟基喹啉水平。OBJECTIVE： To study the effects of Glycyrrhiza uralensis on endogenous metabolites levels of triptolide （TPL） and triptonide （TPN） in rats. METHODS： 160 rats were given G. uralensis [30 g （crude drug）/kg] intragastrically, 2 h later given TPN （2.8 mg/kg） intraperitoneally for consecutive 30 d. 24 h urine were collected for 30 days, and then endogenous metabolites were separated and identified by column chromatograph and spectrum technology. UPLC-Q-TOF/MS was used to determine the common metabolites after giving TPL. 60 rats were randomly divided into TPL blank group, TPL group, G. uralensis＋TPL group, TPN blank group, TPN group, G. uralensis＋TPN group. Route of administration and dosage of treatment groups were same as above groups. TPL blank group and TPN blank group were given corresponding solvent, once a day, for consecutive 7 d. UPLC-Q-TOF/MS was used to determine the endogenous metabolites of TPL and TPN in rats. RESULTS ： Five endogenous metabo- lites were isolated and identified from urine of rats after given TPN, as 1-methylhydantoin, methyl 4-aminonicotinate, 3,4-dihy- dro-6-hydroxy-2 （1H）-quinolinone, 2,6-quinolinediol, 2-quinolone, respectively. Those five metabolites were also found in urine of rats after giving TPN. 1-methylhydantoin in TPL group and 2,6-quinolinediol in TPN group were significantly increased, compared with TPL blank group or TPN blank group （P〈0.05） ; while urine levels of 1-methylhydantoin and 2,6-quinolinediol decreased after TPL or TPN combining with G. uralensis, compared with TPL/TPN blank group, with no significant difference （P〉0,05）. CONCLUSIONS： The above five endogenous metabolites were isolated from rat urine after given TPL or TPN for the first time. The levels of 1-methylhydantoin after giving TPL and 2,6-quinolinediol in urine after giving TPN can be recovered by G. uralensis.

关 键 词：甘草 雷公藤甲素 雷公藤内酯酮 内源代谢物 大鼠 

分 类 号：R917[医药卫生—药物分析学]