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中药复方杞茯地黄丸对链脲佐菌素诱导的糖尿病大鼠的二甲双胍样作用

Metformin-like effects of Quei Fu Di Huang Wan, a Chinese herbal mixture, on streptozotocin-induced diabetic rat.

作者信息

Cheng J T, Liu I M, Chi T C, Su H C, Chang C G

机构信息

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan 70101, R.O.C.

出版信息

Horm Metab Res. 2001 Dec;33(12):727-32. doi: 10.1055/s-2001-19138.

Abstract

Effect on plasma glucose concentration of Quei Fu Di Huang Wan (Quei Fu DHW), the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine, was investigated in diabetic rats deficient in insulin. Changes of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats) receiving repeated oral administration of Quei Fu DHW were determined. Also, the mRNA level (by Northern blotting) and protein level (by Western blotting) of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were measured to compare differences between groups receiving repeated oral administration of Quei Fu DHW, metformin, and two active herbs (Zou Guei or Fuzei) at effective dosages. In STZ-diabetic rats, acute oral administration of Quei Fu DHW decreased the plasma glucose level significantly in a dose-dependent manner from 5 mg/kg to 26.0 mg/kg. Similar treatment with Quei Fu DHW also brought on a plasma glucose-lowering effect in normal rats, although the effectiveness was not as significant as in STZ-diabetic rats. Repeated oral treatment of Quei Fu DHW at 26 mg/kg every 8 h, three times daily for 3 days, produced a plasma glucose-lowering activity similar to that of metformin-treatment in STZ-diabetic rats. Oral administration of Zou Guei (Cinnamomi Cortex) or Fuzei (Aconiti Tuber), the individual constituent of Quei Fu DHW, at the dose of 50 mg/kg into STZ-diabetic rats for 3 days normalized hyperglycemia. Similar to the repeated treatment with Quei Fu DHW, Fuzei at the effective dose reversed the elevated mRNA and protein levels of PEPCK in liver from STZ-diabetic rats. This is consistent with findings that metformin restored the increased gene expression of PEPCK in liver from STZ-diabetic rats. However, the gene expression of PEPCK in STZ-diabetic rats was not influenced by similar treatment with Zou Guei. The present study found that oral administration of Quei Fu DHW could decrease hepatic gluconeogenesis in a way similar to metformin in lowering plasma glucose in diabetic rats lacking insulin. Thus, this preparation may be a helpful adjuvant for the treatment of diabetic disorders in clinical practice.

摘要

研究了中药中广泛用于治疗糖尿病的桂附地黄丸(Quei Fu DHW)对胰岛素缺乏型糖尿病大鼠血浆葡萄糖浓度的影响。测定了链脲佐菌素诱导的糖尿病大鼠(STZ糖尿病大鼠)反复口服桂附地黄丸后血浆葡萄糖的变化。此外,还测量了STZ糖尿病大鼠肝脏中磷酸烯醇式丙酮酸羧激酶(PEPCK)的mRNA水平(通过Northern印迹法)和蛋白质水平(通过Western印迹法),以比较反复口服桂附地黄丸、二甲双胍和两种有效剂量的活性草药(肉桂或附子)的组之间的差异。在STZ糖尿病大鼠中,急性口服桂附地黄丸以剂量依赖性方式显著降低血浆葡萄糖水平,剂量从5mg/kg至26.0mg/kg。用桂附地黄丸对正常大鼠进行类似处理也产生了降低血浆葡萄糖的作用,尽管效果不如STZ糖尿病大鼠显著。以26mg/kg每8小时反复口服桂附地黄丸,每日三次,共3天,在STZ糖尿病大鼠中产生了与二甲双胍治疗相似的降低血浆葡萄糖活性。将桂附地黄丸的单一成分肉桂(Cinnamomi Cortex)或附子(Aconiti Tuber)以50mg/kg的剂量口服给予STZ糖尿病大鼠3天,可使高血糖正常化。与反复用桂附地黄丸治疗相似,有效剂量的附子使STZ糖尿病大鼠肝脏中PEPCK升高的mRNA和蛋白质水平恢复正常。这与二甲双胍恢复STZ糖尿病大鼠肝脏中PEPCK增加的基因表达的研究结果一致。然而,STZ糖尿病大鼠中PEPCK的基因表达不受肉桂类似处理的影响。本研究发现,口服桂附地黄丸可以通过与二甲双胍类似的方式降低肝脏糖异生,从而降低缺乏胰岛素的糖尿病大鼠的血浆葡萄糖。因此,这种制剂在临床实践中可能是治疗糖尿病的有用辅助药物。

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