复方苦参注射液中4种生物碱在大鼠体内组织分布研究  

Tissue distribution of 4 alkaloids of Compound Matrine Injection in rats

作　　者：刘继平[1,2] 黄鑫[3] 薛梅[3] 江振洲[3,4] 张陆勇[3,5] 马世平[1] 

机构地区：[1]中国药科大学中药药理教研室,南京210009 [2]陕西中医学院药理教研室,咸阳712046 [3]中国药科大学江苏省新药筛选中心,南京210009 [4]中国药科大学药物质量与安全预警教育部重点实验室,南京210009 [5]中国药科大学江苏省药效研究与评价服务中心,南京210009

出　　处：《中药药理与临床》2011年第4期74-78,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：十一五"重大新药创制"科技重大专项:超五亿元岩舒大品种技术改造(2008ZX09202-009);陕西省教育厅:复方苦参注射液活性成分Beagle犬体内药动学研究(2010JK498)

摘　　要：目的:建立LC-MS法测定大鼠血浆和其他组织中苦参碱、氧化苦参碱、槐果碱、氧化槐果碱的浓度,研究复方苦参注射液在大鼠体内心、肝、脾、肺、肾等12个脏器组织的分布。方法:在血浆和组织样品中加入内标,用氯仿提取,以甲醇:10 mmolNH4Ac-0.02%HCOOH-水=90:10(v:v);CN柱分离,LC-MS法检测健康大鼠给予复方苦参注射液后3个时间点(15min、1h、4h)的血浆及组织样品中4种生物碱的浓度。结果:在给药后3个时间点,苦参碱和槐果碱在各组织中的分布量依次为:肝>肾/脾>肌肉/肠>肺/胃>心/脑>脂肪/子宫>睾丸;氧化苦参碱和氧化槐果碱在各组织中的分布量依次为:肾/肺>肌肉>肠/胃>心/脾>子宫>脂肪/睾丸>脑/肝;随着时间的推移,苦参碱和槐果碱浓度下降速度明显缓于氧化苦参碱和氧化槐果碱;苦参碱和槐果碱在肝脏分布最多,而氧化苦参碱和氧化槐果碱在肝脏分布最低。结论:复方苦参注射液4种生物碱在组织脏器中的分布,氧化态和非氧化态存在较大差异,尤其在肝脏,氧化苦参碱、氧化槐果碱浓度很低,而苦参碱、槐果碱浓度很高;而且在各组织中苦参碱和槐果碱的浓度显著高于氧化苦参碱和氧化槐果碱,与血浆中的分布相反,说明苦参碱和槐果碱相对于氧化苦参碱和氧化槐果碱而言主要分布于组织脏器中。Objective： LC-MS method was established to determine the concentrations of matrine,oxymatrine,sophocarpine and oxysophocarpine in blood plasma and other organizations of rats.The tissue distribution of Compound Matrine Injection in 12 tissues of rat,such as heart,liver,spleen,lung,kidney and other tissues,was investigated.Method： The samples were extracted by chloroform after adding the internal standard.methanol： 10mmol NH4Ac 0.02% HCOOH water = 90：10（v： v）;CN column separation,detection healthy rats given Matrine Injection time points after 3（15min,1h,4h） in plasma and tissue samples of 4 concentrations of alkaloids.Results： The tissue distribution of matrine,oxymatrine,sophocarpine and oxysophocarpine at 3 time points after administration.The dose distribution order of matrine and sophocarpine in tissues was liver〉kidney / spleen〉 muscle / intestine〉 lung / stomach〉 heart / brain〉 fat / uterus〉 testis;and of oxymatrine and oxysophocarpine was kidney / lung〉 muscle〉 intestine / stomach〉 heart / spleen〉 uterus〉 fat / testis〉 brain / liver.With the development of time,the concentrationes of matrine and sophocarpine were declined more slowly than of oxymatrine and oxysophocarpine;and the dose distribution of matrine and sophocarpine in liver was more than of oxymatrine and oxysophocarpine.Conclusion： Matrine Injection 4 alkaloids in the distribution of organs in the organization,oxidation state and non-oxidized state there is a big difference,especially in the liver,oxymatrine,low concentrations of oxysophocarpine,and matrine sophocarpine high concentrations;and in various tissues and sophocarpine matrine concentration was significantly higher than oxymatrine and oxysophocarpine,and the distribution of plasma contrast,shows the relative matrine and sophocarpine in oxymatrine and in terms of oxysophocarpine mainly distributed in tissues organs.

关 键 词：复方苦参注射液 苦参碱 氧化苦参碱 槐果碱 氧化槐果碱 LC-MS 组织分布 

分 类 号：R285[医药卫生—中药学]