丹参-川芎嗪配伍前后对急性心肌缺血大鼠体内排泄及Ⅱ相代谢酶的影响  

Effect of Salvia miltiorrhiza and ligustrazine before and after compatibility on rat excretions and phaseⅡmetaboling enzymes

作　　者：孙佳[1] 李容 勾健 潘文琪 陆苑[1] 刘春花[4] 黄勇[1] 刘亭[4] SUN Jia;LI Rong;GOU Jian;PAN Wenqi;LU Yuan;LIU Chunhua;HUANG Yong;LIU Ting(Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Pharmacy,Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Clinical Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine Development and Application,Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学、贵州省药物制剂重点实验室,贵州贵阳550004 [2]贵州医科大学药学院,贵州贵阳550004 [3]贵州医科大学临床医学院,贵州贵阳550004 [4]贵州医科大学民族药与中药开发应用教育部工程研究中心&省部共建药用植物功效与利用国家重点实验室,贵州贵阳550004

出　　处：《贵州医科大学学报》2023年第11期1315-1322,共8页Journal of Guizhou Medical University

基　　金：国家自然科学基金项目(81803827);贵州省优秀青年科技人才项目(黔科合平台人才〔2021〕5619);贵州省普通高等学校科技拔尖人才项目(黔教合KY字〔2021〕033);大学生创新创业训练计划项目(S202110660059)。

摘　　要：目的研究丹参-川芎嗪配伍前后对急性心肌缺血(AMI)大鼠体内排泄及Ⅱ相代谢酶的影响。方法通过大鼠皮下注射盐酸异丙肾上腺素复制AMI模型,尾静脉注射参芎葡萄糖注射液(SGI组)、丹参注射液(DGI组)以及川芎嗪注射液(LGI组)后,收集不同时间段的尿液、粪便,UPLC-MS/MS法测定丹参素、川芎嗪的含量;Western blot检测各组大鼠肝脏中尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)和尿苷二磷酸葡萄糖醛酸转移酶1A6(UGT1A6)酶的表达情况。结果丹参素主要经尿液排泄,在尿液中的累积排泄率为31.35%~33.27%,在粪便中的累计排泄率为4.52%~6.08%;川芎嗪在尿液、粪便中的累积排泄率较低,均不足1%;与DGI组相比,SGI组中UGT1A1和UGT1A6的表达增加(P<0.05,P<0.01);与LGI组相比,SGI组中UGT1A6的表达显著增加(P<0.001)。结论配伍后介导川芎嗪Ⅱ相代谢的UGT1A1和UGT1A6酶表达升高,使川芎嗪的原型排泄量降低。Objective To investigate the effect of Salvia miltiorrhiza and ligustrazine before and after compatibility on the excretions in rats with acute myocardial ischemia(AMI).Methods AMI model was established by subcutaneous injection of isoproterenol hydrochloride.Urine and feces were collected at different time periods after rat tail vain injection of Shenxiong glucose injection(SGI group),Danshen glucose injection(DGI group)and Ligustrazine Phosphate Injection(LGI group).UPLC-MS/MS were applied to measure the contents of Salvianic acid A and ligustrazine.Western blot was used to detect the expressions of rat liver uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)and UGT1A1A6 in each group.Results Salvianic acid A was mainly excreted through urine with the cumulative excretion rate ranging from 31.35%to 33.27%,and the cumulative excretion rate in feces ranging from 4.52%to 6.08%.The cumulative excretion rates of ligustrazine in urine and feces were less than 1%.The expression levels of UGT1A1 and UGT1A6 in SGI group were significantly increased when compared to DGI group(P<0.05 and P<0.01,respectively).When compared to LGI group,the UGT1A6 expression in SGI group was significantly elevated(P<0.001).Conclusion The expressions of UGT1A1 and UGT1A6 which mediate the phaseⅡmetabolism of ligustrazine are increased after compatibility,leading to a decrease of prototype excretion amount of ligustrazine.

关 键 词：参芎葡萄糖注射液 配伍 急性心肌缺血 排泄 差异 Ⅱ相代谢酶 

分 类 号：R285[医药卫生—中药学]