Cocktail探针法评价仙茅不同炮制品对CYP450亚型酶的影响  

Effect Evaluation of Different Processed Curculigo Orchioides on Cytochrome P450 Subtypes by Cocktail Probe Drug Method

作　　者：鞠成国[1,2] 李媛媛 王巍 贾天柱[1,2] Ju Chengguo;Li Yuanyuan;Wang Wei;Jia Tianzhu(School of Pharmacy,Liaoning University of Traditional Chinese Medicine,Liaoning Dalian 116600,China;Chinese Materia Medica Processing Engineering Center of Liaoning Province)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600 [2]辽宁省中药炮制工程技术研究中心

出　　处：《中国药师》2021年第8期409-413,共5页China Pharmacist

基　　金：辽宁省自然科学基金项目(编号:20180550241);2019年全国中药特色技术传承人才培训项目(编号:T20194828003)。

摘　　要：目的:研究仙茅不同炮制品对4种大鼠CYP450亚型酶活性的影响。方法:各组大鼠给药1周后给予混合探针药物,不同时间点采集血样,HPLC法检测探针药物在体内的代谢情况,通过DAS3.0软件计算药动学参数并进行统计分析。结果:与空白组相比,各给药组茶碱和氯唑沙宗的t_(1/2)、AUC_((0-∞))和AUC_((0-∞))均显著降低,CLZ/F显著升高(P<0.05);酒仙茅组、萸仙茅组、姜仙茅组氨苯砜的AUC_((0-∞))和AUC_((0-∞))均显著降低,CLZ/F显著升高(P<0.05),而盐仙茅组氨苯砜t_(1/2)、AUC_((0-t))和AUC_((0-∞))均显著升高,Tmax、CLZ/F显著降低(P<0.05);生品组、酒仙茅组、姜仙茅组甲苯磺丁脲的t_(1/2)均显著降低,而盐仙茅组甲苯磺丁脲的t_(1/2)、CLZ/F均显著降低,AUC_((0-t))和AUC_((0-∞))均显著增加(P<0.05)。结论:仙茅各炮制品对CYP1A2及CYP2E1活性有诱导作用;酒、萸、姜制仙茅对CYP3A4活性有诱导作用,盐仙茅对CYP3A4活性有抑制作用;盐仙茅对CYP2C9活性有抑制作用,其余3组对CYP2C9活性无显著影响。Objective: To study the effects of different processed products of Curculigo orchioides on the activity of four subtypes of CYP450 in rats. Methods: Rats in each group were given mixed probe drugs at the first week after administration, blood samples were collected at different time points, the metabolism of probe drugs in rats was detected by HPLC, and the pharmacokinetic parameters were calculated by DAS3.0 software and analyzed statistically. Results: Compared with those in the control group, t_(1/2), AUC_((0-t)) and AUC_((0-∞)) of ophylline and chlorzoxazone were significantly reduced, and CLZ/F was significantly increased(P<0.05);AUC_((0-t)) and AUC_((0-∞)) of dapsone were significantly decreased and CLZ/F was significantly increased in the groups of wine-processed C orchioides, Evodia rutaecarpa-processed C orchioides and ginger juice-processed C orchioides;t_(1/2), AUC_((0-t)) and AUC_((0-∞)) of dapsone were significantly increased and Tmax and CLZ/F were significantly decreased in the group of salt-processed C orchioides(P<0.05);t_(1/2) of tolbutamide was significantly reduced in the groups of raw C orchioides, wine-processed C orchioides and ginger juice-processed C orchioides;t_(1/2) and CLZ/F were significantly decreased and AUC_((0-t)) and AUC_((0-∞)) of tolbutamide were significantly increased in the group of salt-processed C orchioides(P<0.05). Conclusion: All the processed products of C orchioides can induce the activity of CYP1 A2. Wine-processed C orchioides, Evodia rutaecarpa-processed C orchioides and ginger juice-processed C orchioides can induce the activity of CYP3 A4, while salt-processed C orchioides can inhibit the activity of CYP3 A4. Salt-processed C orchioides can induce the activity of CYP2 C9. The other three groups have no significant effects on CYP2 C9 activity.

关 键 词：仙茅 炮制品 COCKTAIL探针药物法 细胞色素P450 

分 类 号：R285.5[医药卫生—中药学]