微透析法研究六味地黄丸在肾阴虚糖尿病大鼠模型的药动学
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摘要
目的利用微透析取样技术,建立六味地黄丸对肾阴虚型糖尿病效应细胞的"剂量-时间-效应"模型,探究有临床意义的最优给药方案。方法分离并培养肾阴虚型糖尿病大鼠模型的肝细胞、脂肪细胞和胰岛β细胞,实验验证后选取药物反应最大的胰岛β细胞作为效应细胞。用不同剂量的六味地黄丸喂服模型大鼠,微透析法采集透析液并对效应细胞进行处理,检测效应细胞的变化情况。结果胰岛β细胞对六味地黄丸透析液的反应程度显著高于肝细胞和脂肪细胞(P<0.01),故选择胰岛β细胞为效应细胞;给药间隔时间为12h,每次剂量为0.15mg,治疗效果最好(P<0.01)。结论此方案为六味地黄丸治疗肾阴虚型糖尿病的最优给药方案。
Objective To study the pharmacokinetics of Liuwei Dihuang Pills in kidney Yin deficiency diabetes mellitus rats model by microdialysis and to explore the clinical significance of the optimal dosing regimen.Methods The hepatocytes,adipocytes and pancreatic isletβcells of kidney Yin deficiency type of diabetic rats were isolated and cultured.After the test,the isletβcells with the largest drug reaction were selected as effector cells.The model rats were fed with different doses of Liuwei Dihuang Pills.The dialysis fluid was collected by microdialysis and the effector cells were treated to detect the changes.Results Isletβ-cell response to Liuwei Dihuang Pills dialysate was significantly higher than that of hepatocytes and adipocytes(P<0.01),so the isletβcells were selected as effector cells.The optimal dose of Liuwei Dihuang Pills for the treatment of kidney Yin deficiency type diabetes mellitus was obtained after 12 hof administration with the best dose of 0.15 mg one times(P<0.01).Conclusion This program is the optimal dosage regimen for Liuwei Dihuang Pills in the treatment of kidney Yin deficiency type diabetes.
Objective To study the pharmacokinetics of Liuwei Dihuang Pills in kidney Yin deficiency diabetes mellitus rats model by microdialysis and to explore the clinical significance of the optimal dosing regimen.Methods The hepatocytes,adipocytes and pancreatic isletβcells of kidney Yin deficiency type of diabetic rats were isolated and cultured.After the test,the isletβcells with the largest drug reaction were selected as effector cells.The model rats were fed with different doses of Liuwei Dihuang Pills.The dialysis fluid was collected by microdialysis and the effector cells were treated to detect the changes.Results Isletβ-cell response to Liuwei Dihuang Pills dialysate was significantly higher than that of hepatocytes and adipocytes(P<0.01),so the isletβcells were selected as effector cells.The optimal dose of Liuwei Dihuang Pills for the treatment of kidney Yin deficiency type diabetes mellitus was obtained after 12 hof administration with the best dose of 0.15 mg one times(P<0.01).Conclusion This program is the optimal dosage regimen for Liuwei Dihuang Pills in the treatment of kidney Yin deficiency type diabetes.
引文
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[12]谭俊珍,李庆雯,范英昌,等.六味地黄丸对糖尿病大鼠血糖和血脂的影响[J].天津中医药大学学报,2007,26(4):196-198.
[13]董冉冉,王萌,刘志东,等.微透析技术在中药成分体内分析研究中的应用[J].中草药,2015,46(20):3117-3124.
[2] Akram T Kharroubi,Hisham M Darwish.Diabetes mellitus:the epidemic of the century[J].World J Diabet,2015,6(6):850-867.
[3]杨海涛,王广基.毛细管电泳与微透析技术在药物动力学中的应用[J].西北药学杂志,2000,15(3):136-137.
[4]郭啸华,刘志红,李恒,等.高糖高脂饮食诱导的2型糖尿病大鼠模型及其肾病特点[J].中国糖尿病杂志,2002,10(5):290-294.
[5]叶娟,王群,付溪,等.原代大鼠肝细胞分离及培养鉴定[J].实用儿科临床杂志,2012,27(7):531-533.
[6]刘佳,侯莉莉.大鼠原代肝细胞分离培养的实验研究[J].现代医药卫生,2011,27(22):3361-3363,3521.
[7]姜爽.黄连多糖的提取、分离及抗大鼠2型糖尿病作用的实验研究[D].长春:吉林大学,2013.
[8]刘玉溥,吕庆国,童南伟.大鼠胰岛β细胞分离与原代培养方法探讨[J].四川大学学报:医学版,2009,40(1):153-156.
[9] D Papadopoulos,A Filippidis,G Krommidas,et al.Regional cerebral blood flow and cellular environment in subarachnoid hemorrhage:a thermal doppler flowmetry and microdialysis study[J].Neurol Neurochir Pol,2017,51(1):66-71.
[10]Wang C R,Hu C,Zhang R,et al.Association of a common haplotype of hepatocyte nuclear factor 1αwith type2diabetes in Chinese population[J].Biomed Environment Sci,2007,20(1):41-46.
[11]孙颖,刘红利,崔雯雯,等.中药对胰岛β细胞的保护机制研究概述[J].中国实验方剂学杂志,2015,21(18):215-219.
[12]谭俊珍,李庆雯,范英昌,等.六味地黄丸对糖尿病大鼠血糖和血脂的影响[J].天津中医药大学学报,2007,26(4):196-198.
[13]董冉冉,王萌,刘志东,等.微透析技术在中药成分体内分析研究中的应用[J].中草药,2015,46(20):3117-3124.