槐果碱体内药动学和体外抗肿瘤研究  

Study of Pharmacokinetic and Anti-tumor Effect of Sophocarpine

作　　者：杨晓艺[1] 曾诚[1] 李建光[1] 

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011

出　　处：《中药新药与临床药理》2017年第5期644-648,653,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81560687);新疆研究生科研创新项目(XJGRI2015073)

摘　　要：目的建立大鼠颈静脉置管模型,探讨槐果碱在大鼠体内的药代动力学,并初步考察槐果碱对体外人宫颈癌细胞增殖影响。方法大鼠灌胃槐果碱(30,60,120 mg·kg^(-1)),HPLC法测定大鼠灌胃给药后不同时间点血浆中槐果碱的浓度,并采用Kinetica 4.4.1软件计算药代动力学参数。体外培养人宫颈癌Hela和Siha细胞株,分别加入终浓度为0.625,1.25,2.5,5,10,20 mmol·L^(-1)的槐果碱,MTT法检测槐果碱对Hela和Siha细胞活性的影响,倒置显微镜下观察细胞形态变化。结果大鼠灌胃给药后,槐果碱(30,60,120 mg·kg^(-1))在大鼠体内呈二室分布,C_(max)分别为(54.42±8.35),(91.16±13.72)和(157.64±26.85)μg·mL^(-1);T_(max)分别为(11.07±2.27),(8.47±1.13)和(13.53±3.88)min;t1/2分别为(15.95±0.93),(28.34±1.27)和(22.25±2.32)min;AUC分别为(812.79±65.81),(1571.92±172.62)和(2278.87±228.12)min·μg·mL^(-1)。体外细胞实验结果显示,不同浓度的槐果碱能明显抑制Hela和Siha细胞增殖,且呈时间和浓度依赖性。结论槐果碱在大鼠体内具有口服吸收快、作用时间长和消除缓慢等特点,同时,对人宫颈癌细胞HeLa、Siha细胞均有显著抑制作用。Objective To establish the rat jugular vein catheterization model for pharmacokinetics study of Sophocarpine （SOP） in rats; and evaluate the in vitro anticancer effect of SOP. Methods Rats were given intragastric administration of SOP（30, 60, 120 mg·kg^-1） , and then the blood was sampled at different time points. HPLC method was used to analyze the plasma concentration of SOP, and pharmaeokinetic parameters were calculated by compartmental model in Kinetica 4.4.1 software. Hela and Siha cell were cultured for 24 h in vitro, then cocuhrued with SOP at the concentration of 0.625, 1.25, 2.5, 5, 10 and 20 mmol·L^-1 for 24, 48, 72 and 96 h, respectively. The proliferation of cells was detected by MTT. Morphological change of cells was observed under inverted microscope. Results SOP was found to fit a two-compartment open model in rat, and the main pharmacokinetic parameters Cmax, Tmax tin and AUC of SOP were （54.42 ±8.35）, （91.16 ± 13.72） and （157.64 ± 26.85） μg·mL^-1; （11.07 ± 2.27）, （8.47 ± 1.13） and （13.53±3.88） rain; （15.95±0.93）, （28.34± 1.27） and （22.25±2.32） min; （812.79± 65.81）, （1 571.92± 172.62） and （2 278.87±228.12） min·μg· mL^-l. Hela and Siha cells were treated with different concentration of SOP at different time points; the proliferation of cells was significantly inhibited by SOP in a time and dose-dependent manner. Conclusion SOP used for rats shows a rapid absorption, longer duration and slow elimination process. Meanwhile, it＇ s feasible and meaningful to develop an oral dosage form of SOP.

关 键 词：槐果碱 苦豆子 药物动力学 人宫颈癌细胞 抗肿瘤 

分 类 号：R285.5[医药卫生—中药学]