利用液质联用技术分析干姜对乌头类生物碱在大鼠肠内吸收的影响  

Study on the Influence of Rhizoma Zingiberis on the Absorptive Profile of Aconite Alkaloids in the Rat Gut Sacs by Ultra Performance Liquid Chromatography-Mass Spectrometry

作　　者：辛杨[1,2] 皮子凤[1] 宋凤瑞[1] 刘志强[1] 刘淑莹[1] 

机构地区：[1]中国科学院长春应用化学研究所,长春1300221 [2]中国科学院研究生院,北京100039

出　　处：《化学学报》2012年第5期551-560,共10页Acta Chimica Sinica

基　　金：国家"973"计划中医理论专项基金(No.2011CB505300-05);国家自然科学基金(Nos.81073040;30472134;21175127);吉林省科技厅项目(No.YYZX201131)资助项目~~

摘　　要：为从吸收的角度考察干姜对乌头类双酯型生物碱的解毒机理,采用外翻肠囊法展开实验.利用超高液相与三重四极杆质谱联用技术定量检测双酯型生物碱成分,采用标准曲线法计算乌头碱、中乌头碱、次乌头碱在肠囊内吸收的绝对含量,采用质谱峰面积直接分析其它双酯型生物碱的相对变化,结果加入干姜提取液后,乌头碱、中乌头碱、次乌头碱的单位肠管面积累计吸收量均降低,10-羟基中乌头碱的的累积峰面积降低;加入维拉帕米后,双酯型生物碱的单位肠管面积累计吸收量及累积峰面积均增加;向含有地高辛的肠营养液中加入干姜提取液后,地高辛在各实验时间点的单位肠管面积累计吸收量均降低,根据以上结果推测干姜抑制乌头类双酯型生物碱在大鼠肠囊内吸收的可能机制是通过诱导肠内P-葡糖蛋白,从而抑制作为P-葡糖蛋白底物的双酯型生物碱的吸收,最终起到减毒作用.Everted rat gut sac model was used to carry out the experiments about detoxification mechanism of Rhizoma Zingiberis on the diester-aconite alkaloids in Radix Aconiti. All the diester-aconite alkaloids were detected by Waters Ultra Performance Liquid Chromatography coupled with triple quadrupole Mass Spectrometry. Content of aconitine, mesaconitine and hypaconitine were calculated by standard curve method and other diester-aconite alkaloids were calculated by peak area. Results showed that the accumulative absorptive content of aconitine, mesaconitine, hypaconitine and the peak area of 10-OH-mesaconitine in unit area of the rat gut sac decreased when the extract of Rhizoma Zingiberis was added into K-R solution contained the exact of Radix Aconiti, and that increased when verapamil was added into K-R solution contained the exact of Radix Aconiti, which indicated the diester-aconite alkaloids might be the potential sub- strate of P-glycoprotein （P-gp）. The accumulative content of digoxin in unit area of the rat gut sac decreased when the extract of Rhizoma Zingiberis was added into the intestinal nutritious solution contained digoxin, which indicated the extract of Rhizoma Zingiberis might be the revulsant of P-glycoprotein. On the basis of the above results, it could be concluded that the possible mechanism of the inhibition of the extract of Rhi-zoma Zingiberis on the absorption of the aconite Zingiberis which served as the potential revulsant iting the activity of the intestinal P-gp. alkaloids in the rat gut sacs was the extract of Rhizoma could inhibit the absorption of aconite alkaloids by inhib-iting the activity of the intestinal P-gp.

关 键 词：外翻肠囊法 乌头类生物碱 干姜 液质联用 P-葡糖蛋白 

分 类 号：R285.5[医药卫生—中药学]