雌激素对去卵巢大鼠肝细胞胰岛素受体底物-1和2表达的影响

Effect of estrogen on the expressions of insulin receptor substrate-1 and insulin receptor substrate-2 in hepatic cells of ovariectomized rats

目的观察雌激素对去卵巢大鼠肝细胞胰岛素受体底物-1(IRS-1)和胰岛素受体底物-2(IRS-2)表达的影响,以探讨其改善胰岛素抵抗的机制。方法取6周SD雌性大鼠随机分为3组:假手术组(Sham组)、手术组(OVX组)和戊酸雌二醇组(E_2组),E_2组每天灌胃戊酸雌二醇水溶液(1 mg/kg),而其他组给予相应体积的蒸馏水,连续给药12周。然后采用葡萄糖氧化酶法测定血糖,实时荧光定量PCR法检测肝细胞IRS-1和IRS-2 mRNA的表达,免疫组织化学法检测肝细胞IRS-1和IRS-2蛋白的表达。结果 OVX大鼠终末体重、肝重、内脏脂肪指数KITT显著高于Sham组,而葡萄糖利用常数KITT显著低于Sham组(P<0.05);与OVX组大鼠相比,E_2组大鼠终末体重、肝重、内脏脂肪指数显著降低,而葡萄糖利用常数显著升高(P<0.05);免疫组化结果显示,OVX大鼠肝组织IRS-1、IRS-2表达阳性细胞数目及染色程度较Sham组显著减少,而雌激素替代治疗后肝组织IRS-2阳性表达细胞数目及染色程度显著改善,但IRS-1改善不显著;OVX大鼠肝细胞IRS-1和IRS-2mRNA表达水平显著低于Sham组,而E_2组大鼠IRS-1和IRS-2 mRNA表达水平显著高于OVX组(P<0.05)。结论雌激素可上调去卵巢大鼠肝细胞IRS-1和IRS-2的表达水平,进而改善胰岛素抵抗。

Objective To observe the effect of estrogen on the expressions of insulin receptor substrate-1（ IRS-1） and insulin receptor substrate-2（ IRS-2） in hepatic cells of ovariectomized rats,explore the mechanism of improving insulin resistance. Methods Female SD rats（ 6 weeks） were randomly divided into three groups： sham-operation group（ Sham group）,ovariectomy group（ OVX group） and estradiol valerate group（ E_2group）. The rats in E_2 group were treated by intragastric administration of estradiol valerate（ 1 mg / kg）,while the rats in other groups were treated by intragastric administration of distilled water of the same volume,the therapy lasted for 12 weeks.Blood glucose was measured by glucose oxidase method,fluorescence quantitative RT-PCR was used to detect the expressions of IRS-1 and IRS- 2 mRNA in hepatic cells,immunocytochemichal staining was used to detect the expressions of IRS- 1 and IRS- 2 proteins.Results Terminal weight,liver weight and visceral fat index in OVX group were significantly higher than those in Sham group,but KITT in OVX group was significantly lower than that in Sham group（ P〈0. 05）. Compared with OVX group,terminal weight,liver weight and visceral fat index in E_2 group decreased significantly,but KITT increased significantly（ P〈0. 05）. Immunohistochemistry showed that the numbers of IRS-1 and IRS-2 positive cells and staining degrees in OVX group were significantly lower than those in Sham group,but after estrogen replacement therapy,the number of IRS-2 positive cells and staining degree in OVX group were improved significantly,the changes were not obvious in IRS-1. The expression levels of IRS-1 and IRS-2 mRNA in OVX group were significantly lower than those in Sham group,but the expression levels of IRS-1 and IRS-2 mRNA in E_2 group were significantly higher than those in OVX group（ P〈0. 05）. Conclusion Estrogen can upregulate the expression levels of IRS-1 and IRS-2 in hepatic cells of ovariectomized rats and further improve insulin resistance.