二甲双胍改善去势大鼠胰岛素抵抗的机制研究

Metformin Mechanism of Insulin Resistance in Ovariectormized Female Rats

关键词:  二甲双胍  胰岛素抵抗  肿瘤坏死因子-α  细胞因子信号转导抑制因子-3

Key words:  metformin  insulin resistance  TNF-α  SOCS-3

摘要:

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。

Abstract:

OBJECTIVE To investigate the improvement effect and mechanism of metformin(MF) on insulin resistance in castrated female rats. METHODS The levels of serum estradiol(E₂), progesterone (P) and insulin (INS) were determined by radioimmunoassay method. Tumor necrosis factor-a (TNF-α) level was measured by enzyme-linked immunosorbent assay. Gene expression of pancreas islet suppressor of cytokine sighting-3(SOCS-3) was determined by using reverse transcriptase polymerase chain reaction. RESULTS Compared with NS group, the serum E₂ and P content in OVX group were significantly decreased, the TNF-α, INS content were significantly increased , while the SOCS-3 mRNA expression of pancreas islets were significantly increased(P<0.01). Compared with the OVX group, MF low group has no significant change. Serum E₂ and P content were significantly increased (P<0.05) in MF high group. The TNF-α, INS content significantly decreased (P<0.05 or P<0.01), while the SOCS-3 mRNA expression of islets were significantly decreased (P<0.01). CONCLUSION Long-term with a large dose of MF 270 mg·kg^-1·d^-1can improve ovariectormized rats insulin resistance phenomenon. The mechanism may be related with the decreased of TNF-α and SOCS-3 mRNA expression of islets.