Hu Xiaochen, Sato Juichi, Bajotto Gustavo, Khookhor Oyun, Ohsawa Isao, Oshida Yoshiharu, Sato Yuzo
Department of General Medicine, Nagoya University Hospital, Nagoya, Japan.
Nagoya J Med Sci. 2010 Feb;72(1-2):35-42.
Goshajinkigan (GJG), an aqueous extract of a combination of 10 herbal medicines, is widely used for the treatment of diabetic neuropathy in Japan. In this study, the effect of GJG on insulin-induced glucose disposal in normal and streptozotocin (STZ) diabetic rats was analyzed using the euglycemic clamp technique. Male Wistar rats, aged 9 weeks, were randomly assigned to six groups: group NS, normal rats receiving saline; group NG, normal rats receiving GJG (800 mg x kg(-1) x day(-1), p.o.); group NGL, normal rats receiving GJG + N(G)-monomethyl-L-arginine (L-NMMA, 1 mg x kg(-1) x min(-1), i.v.); group DS, diabetic rats receiving saline; group DG, diabetic rats receiving GJG; group DGL, diabetic rats receiving GJG + L-NMMA. After daily oral administrations of saline or GJG for one week, euglycemic clamp experiments were performed. The metabolic clearance rates of glucose (MCR) in the DS, DG, and DGL groups (8.7 +/- 2.9, 18.2 +/- 2.5, and 8.1 +/- 1.8 ml x kg(-1) x min(-1), respectively) were significantly lower than those in the NS, NG, and NGL groups (24.1 +/- 4.5, 24.5 +/- 3.1, and 22.2 +/- 2.1 ml x kg(-1) x min(-1), respectively). In addition, the MCR in the DG group was significantly higher than that in the DS and DGL groups, while no significant difference was detected among the NS, NG, and NGL groups. Furthermore, the amelioration of insulin resistance by GJG in diabetic rats was hampered by L-NMMA infusion. These results suggest that daily GJG administrations ameliorate insulin resistance in STZ-diabetic rats, and that the nitric oxide pathway may mediate the effect of GJG.
汉方制剂“五物人参汤”（GJG）由10种草药组合而成的水提取物，在日本被广泛用于治疗糖尿病性神经病变。在本研究中，采用正常血糖钳夹技术分析了GJG对正常大鼠和链脲佐菌素（STZ）诱导的糖尿病大鼠胰岛素诱导的葡萄糖处置的影响。9周龄雄性Wistar大鼠被随机分为6组：NS组，正常大鼠接受生理盐水；NG组，正常大鼠接受GJG（800mg·kg⁻¹·d⁻¹，口服）；NGL组，正常大鼠接受GJG + N(G)-单甲基-L-精氨酸（L-NMMA，1mg·kg⁻¹·min⁻¹，静脉注射）；DS组，糖尿病大鼠接受生理盐水；DG组，糖尿病大鼠接受GJG；DGL组，糖尿病大鼠接受GJG + L-NMMA。每日口服生理盐水或GJG一周后，进行正常血糖钳夹实验。DS组、DG组和DGL组的葡萄糖代谢清除率（MCR）（分别为8.7±2.9、18.2±2.5和8.1±1.8ml·kg⁻¹·min⁻¹）显著低于NS组、NG组和NGL组（分别为24.1±4.5、24.5±3.1和22.2±2.1ml·kg⁻¹·min⁻¹）。此外，DG组的MCR显著高于DS组和DGL组，而NS组、NG组和NGL组之间未检测到显著差异。此外，L-NMMA输注阻碍了GJG对糖尿病大鼠胰岛素抵抗的改善作用。这些结果表明，每日给予GJG可改善STZ糖尿病大鼠的胰岛素抵抗，并且一氧化氮途径可能介导了GJG的作用。
