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

Study on pharmacokinetics of Liuwei Dihuang Pills in kidney Yin deficiency diabetes mellitus rats model by microdialysis

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 h of 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.