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目的探讨二甲双胍(MF)对去势雌性大鼠胰岛素抵抗的改善作用及机制。方法采用放射免疫分析法RIA测定血清雌二醇(E2)、孕酮(P)、胰岛素(INS)的水平,采用酶联免疫吸附试验ELISA测定肿瘤坏死因子-α(TNF-α)的水平,采用逆转录聚合酶链反应RT-PCR测定胰岛细胞因子信号转导抑制因子-3(suppressor of cytokine sighting-3,SOCS-3)的基因表达。结果与假手术(SHAM)组比较,去势(OVX)模型组E2、P的含量显著降低,而TNF-α、INS含量则明显升高,同时大鼠胰岛SOCS-3基因表达明显上调(P<0.01)。与OVX组比较,去势二甲双胍低剂量(MF低)组无显著影响,去势二甲双胍高剂量(MF高)组E2、P含量则显著升高(P<0.05),INS含量明显降低(P<0.05或P<0.01),大鼠胰岛SOCS-3基因表达明显下调(P<0.01)。结论长期大剂量使用MF可以改善去势大鼠的胰岛素抵抗现象,其机制可能与下调TNF-α和胰岛SOCS-3基因表达有关。
Objective To investigate the effect and mechanism of metformin (MF) on insulin resistance in ovariectomized female rats. Methods The levels of serum estradiol (E2), progesterone (P) and insulin (INS) were determined by radioimmunoassay. The levels of tumor necrosis factor-α (TNF- Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression of isorvastatin cytokine sighting-3 (SOCS-3). Results Compared with SHAM group, the levels of E2 and P in OVX model group were significantly decreased, while the levels of TNF-α and INS were significantly increased, while the expression of SOCS-3 gene in pancreatic islet group was significantly increased (P <0.01). Compared with OVX group, there was no significant effect of castrated metformin low dose (MF) group and E2 and P levels of castrated metformin high dose (MF) group were significantly increased (P <0.05), INS content was significantly decreased (P < 0.05 or P <0.01). The expression of SOCS-3 gene was significantly down-regulated in rat islets (P <0.01). Conclusion Long-term high-dose of MF can improve insulin resistance in ovariectomized rats, which may be related to down-regulation of TNF-α and SOCS-3 gene expression in islets.