Abstract: Objective　To investigate the effect of type Ⅰ interferon (IFNα-2b) on the hypoglycemic effect of metformin in diabetic rat models, so as to provide experimental evidence for rational clinical medication.Methods　Sixty SD rats aged 6-8 weeks were used in this study. Among them, fifty-four rats received intraperitoneal injection of streptozotocin (STZ) to establish diabetic models. After successful modeling, 30 rats were randomly divided into 5 groups (n=6) according to the dose of metformin, control group 1, 0.5 g/kg group, 1.0 g/kg group, 1.5 g/kg group and 2.0 g/kg group. Blood glucose changes were observed, and the optimal dose of metformin was determined based on the correlation between blood glucose variation and drug dosage. Subsequently, unmodeled rats were used as the blank group (n=6), and the remaining 24 successfully modeled rats were randomly divided into control group 2, IFNα-2b group, metformin group and IFNα-2b + metformin group (n=6). Rats in the metformin group and IFNα-2b + metformin group were intragastrically administered with 1.0 g/kg metformin. Rats in the IFNα-2b group and IFNα-2b + metformin group were intraperitoneally injected with 4×105 IU/kg IFNα-2b. Blood glucose levels in rats were monitored.Results　The hypoglycemic effect of metformin on diabetic rats showed an obvious dose-dependent manner (R2=0.9109), and 1.0 g/kg was determined as the optimal dose of metformin. After administration, blood glucose levels in the metformin group were significantly lower than those before treatment (P<0.01). However, no significant decrease in blood glucose was observed in the IFNα-2b group and IFNα-2b + metformin group than those before treatment. The differences between these two groups and the metformin group were statistically significant (P<0.01).Conclusion　In the diabetic rat model established in this study, IFNα-2b can significantly inhibit the hypoglycemic effect of metformin.

Key words: metformin, type I interferon, diabetes mellitus, rat model

摘要： 目的　探讨Ⅰ型干扰素(IFNα-2b)对糖尿病大鼠模型中二甲双胍降糖效应的影响,为临床合理用药提供实验 依据。方法　选取60只6~8周龄SD大鼠作为实验对象,其中54只采用腹腔注射链脲佐菌素(STZ)法构建糖尿 病大鼠模型。造模成功后,选取其中30只大鼠,按二甲双胍给药剂量随机分为5组(n=6),分别为对照组1、 0.5 g/kg组、1.0 g/kg组、1.5 g/kg组及2.0 g/kg组,观察大鼠血糖变化情况,并依据血糖变化与给药剂量的相关 性,确定二甲双胍的最适给药剂量。随后,以未造模大鼠为空白组(n=6),将其余24只造模成功大鼠随机分为对 照组2、IFNα-2b组、二甲双胍组及IFNα-2b+二甲双胍组(n=6)。二甲双胍组及IFNα-2b+二甲双胍组采用灌胃方 式给予1.0 g/kg二甲双胍;IFNα-2b组及IFNα-2b+二甲双胍组采用腹腔注射方式给予40万IU/kg IFNα-2b,观察大 鼠血糖变化情况。结果　二甲双胍对糖尿病大鼠的降糖作用呈明显剂量依赖性(R2=0.9109),确定1.0 g/kg为二 甲双胍最适给药剂量。给药后,二甲双胍组大鼠血糖水平较给药前显著降低(P<0.01);而IFNα-2b组及IFNα-2b+ 二甲双胍组大鼠血糖与给药前比较无显著下降,两组与二甲双胍组比较,差异均有统计学意义(P<0.01)。 结论　本实验建立的糖尿病大鼠模型中,IFNα-2b可显著抑制二甲双胍的降糖效应。

关键词: 二甲双胍, Ⅰ型干扰素, 糖尿病, 大鼠模型