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绿茶中咖啡因在正常和糖尿病认知功能障碍大鼠体内的药代动力学及药效学分析
引用本文:刘国旗,刘声菊,王娇,李莉,李兴,伍庆,潘卫. 绿茶中咖啡因在正常和糖尿病认知功能障碍大鼠体内的药代动力学及药效学分析[J]. 中国实验方剂学杂志, 2018, 24(11): 99-104
作者姓名:刘国旗  刘声菊  王娇  李莉  李兴  伍庆  潘卫
作者单位:贵州医科大学医学检验学院;贵州师范大学山地环境重点实验室;贵州医科大学附属医院贵州省产前诊断中心
基金项目:国家自然科学基金地区基金项目(81560720,81560138);喀斯特地区生物与信息技术协同创新中心项目(黔教合协同创新字[2014]04)
摘    要:目的:在建立气相色谱法(GC)方法学的基础上,比较绿茶中咖啡因在正常和糖尿病认知功能障碍大鼠体内的血药浓度,并验证其对糖尿病认知功能障碍的影响。方法:采用链脲佐菌素(STZ)一次性腹腔注射(剂量50 mg·kg-1)复制糖尿病模型,模型复制成功后灌胃咖啡因和绿茶浸出液进行干预,并且每3周测定1次血糖值,诱导第12周时Morris水迷宫试验检测认知功能,选择HP-5色谱柱,二阶升温程序,流速1.0 m L·min-1,分流比10∶1,氢火焰离子化检测器(FID),检测器温度和进样口温度均为250℃,载气为氮气的色谱条件进行咖啡因在正常和糖尿病认知功能障碍大鼠体内的药代动力学研究,运用透射电镜观察神经元细胞的超微结构。结果:咖啡因的线性范围1.28~128 mg·L-1(R2=0.998),最低检测限和最低定量限分别为0.7,1.28 mg·L-1,日内和日间精密度均8.0%,提取回收率和方法回收率均90%。咖啡因在正常和糖尿病认知功能障碍大鼠体内的药时曲线下面积(AUC0-t)分别为(46.71±4.25),(61.2±5.44)mg·h·L-1,半衰期(t1/2)分别为(2.82±0.38),(3.71±0.13)h,药峰浓度(Cmax)分别为(13.25±2.02),(17.12±1.08)mg·L-1,清除率(CL)分别为(0.43±0.08),(0.33±0.07)L·kg-1·h-1。与模型组比较,咖啡因组和绿茶组血糖下降、认知能力和神经元细胞超微结构得到改善。结论:咖啡因在正常和糖尿病认知功能障碍大鼠体内的代谢存在差异,且具有改善糖尿病认知功能障碍的功效,这为绿茶和咖啡因临床用于防止糖尿病认知障碍提供了一定理论依据。

关 键 词:绿茶  咖啡因  糖尿病认知功能障碍  药代动力学  药效学  盐酸伪麻黄碱  血脑屏障
收稿时间:2017-09-26

Pharmacokinetics and Pharmacodynamics of Caffeine from Green Tea in Normal and Diabetic Cognitive Dysfunction Rats
LIU Guo-qi,LIU Sheng-ju,WANG Jiao,LI Li,LI Xing,WU Qing and PAN Wei. Pharmacokinetics and Pharmacodynamics of Caffeine from Green Tea in Normal and Diabetic Cognitive Dysfunction Rats[J]. China Journal of Experimental Traditional Medical Formulae, 2018, 24(11): 99-104
Authors:LIU Guo-qi  LIU Sheng-ju  WANG Jiao  LI Li  LI Xing  WU Qing  PAN Wei
Affiliation:School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, China,School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, China,Key Laboratory for Mountainous Environment, Guizhou Normal University, Guiyang 550001, China,School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, China,School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, China,Key Laboratory for Mountainous Environment, Guizhou Normal University, Guiyang 550001, China and School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, China;Guizhou Prenatal Diagnostic Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Abstract:Objective: To establish a gas chromatography (GC) method for comparison of drug concentration in plasma of caffeine in normal and diabetic cognitive dysfunction rats after intragastric administration of green tea extract,and further validate its influence on diabetic cognitive dysfunction. Method: Diabete models were copied by one-time intraperitoneal injection streptozotocin (STZ) with dose of 50 mg·kg-1,after successful replication of the model,diabetic rats were intervened by gavage of caffeine and green tea extract,respectively;blood glucose value was determined once every three weeks,cognitive function was analyzed with Morris water maze experiment at the 12 week,and then GC was used to study on pharmacokinetics of caffeine in normal and diabetic cognitive dysfunction rats,and transmission electron microscopy was employed to observe ultrastructure of neurons. Result: The linear range of caffeine was 1.28-128 mg·L-1(R2=0.998),the minimum test limit and the minimum quantitative limit were 0.7,1.28 mg·L-1,respectively.The RSD of inter-day and intra-day precision were less than 8.0%,the average method and extraction recoveries were more than 90%.The area under the curve (AUC0-t) of caffeine in normal and diabetic cognitive dysfunction rats were(46.71±4.25),(61.2±5.44) mg·h·L-1,the half-life (t1/2) were (2.82±0.38),(3.71±0.13) h,the peak plasma concentration (Cmax) were (13.25±2.02),(17.12±1.08) mg·L-1,the clearance (CL) were (0.43±0.08),(0.33±0.07) L·kg-1·h-1,respectively.Compared with the model group,the blood glucose of caffeine group and green tea extract group dropped,their cognitive ability and ultrastructure of neurons were improved. Conclusion: Metabolism of caffeine in normal and diabetic cognitive dysfunction rats has difference,and it can improve the diabetic cognitive dysfunction.This study provides a theoretical basis for clinical use of green tea and caffeine in preventing diabetic cognitive dysfunction.
Keywords:green tea  caffeine  diabetic cognitive dysfunction  pharmacokinetics  pharmacodynamics  pseudoephedrine hydrochloride  blood-brain barrier
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