龙胆碱在大鼠体内的药动学特征及透过血脑屏障的研究  

Pharmacokinetic Characteristics and Blood-brain Barrier Transport of Gentianine in Rats

作　　者：刘学伟[1] 刘天宇[1] 刘树民[1] 汤青[1] 

机构地区：[1]黑龙江中医药大学中医药研究院,哈尔滨市150040

出　　处：《中国药房》2011年第19期1734-1737,共4页China Pharmacy

基　　金：国家教育部科技重点项目(207029)

摘　　要：目的:利用高效液相色谱(HPLC)法研究龙胆碱的药动学特征及判断其是否透过血脑屏障。方法:大鼠经尾静脉注射龙胆碱后,断尾取血,离心后分离血清,经固相萃取柱(SPE)沉淀蛋白。色谱柱为Diamonsil-C1(8250mm×4.6mm,5μm),流动相为甲醇-水(梯度洗脱),全波长扫描,流速为1.0mL·min-1。在此基础上,采用腹腔注射龙胆碱后断头取脑,用HPLC法测定脑中龙胆碱含量,依据龙胆碱给药剂量与脑内含量的值推算龙胆碱是否透过血脑屏障。结果:龙胆碱线性回归方程为A=2.445×107c-44388.6(r=0.9997,n=6),表明龙胆碱血清浓度在3.125×10-4～0.1mg·mL-1范围内与峰面积积分值线性关系良好;最低检出浓度为0.02μg·mL-1;主要药动学参数t1/2a=8.62min,t1/2β=116.64min,AUC=3.57mg·min·mL-1,CL(s)=28.05mg2·kg-1·mL-1·min-1。在大鼠脑内能检测到龙胆碱,且其含量随给药剂量增加而增加。结论:静脉注射龙胆碱的大鼠其体内药动学呈开放二室模型;龙胆碱能透过血脑屏障。OBJECTIVE：To study the pharmacokinetic characteristics and blood-brain barrier transport of gentianine in rats by HPLC. METHODS：Rats were treated by caudal vein injection of gentianine,then cut the tails,the blood was collected into centrifuge tube. Serum was separated by centrifugation and SPE method was used to deposit proteins. The separation was performed on Diamonsil-C18（250 mm×4.6 mm,5 μm） column with mobile phase consisted of methanol-water（gradient elution） . We performed a whole wavelength scanning at flow rate of 1.0 mL·min-1. Then those rats were treated with gentianine intraperitoneally and decapitated. The concentration of gentianine was determined by HPLC. Whether gentianine delivered through blood-brain barrier was evaluated according to the dose of gentianine and the content of it in cerebral tissue. RESULTS：The linear regression equation of gentianine was A=2.445×10-7c-44 388.6（r=0.999 7,n=6） . The linear range of gentianine was 3.125×10-4～0.1 mg·mL-1,and the lowest detection limit of gentianine was 0.02 μg·mL-1. Main pharmacokinetics parameters of gentianine were t1/2α=8.62 min,t1/2β=116.64 min,AUC=3.57 mg·min·mL-1,CL（s） =28.05 mg2·kg-1·mL-1·min-1;Gentianine could be determined in cerebral tissue of rats,and the content of it in cerebral tissue increased as long as the dose of gentianine increased. CONCLUSION：The pharmacokinetic procedure of gentianine with intravenous administration could be described as open two-compartment model;gentianine can deliver across the blood-brain barrier.

关 键 词：龙胆碱 药动学 高效液相色谱法 血脑屏障 

分 类 号：R285[医药卫生—中药学] R97[医药卫生—中医学]