论文部分内容阅读
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 effects of estrogen on the expression of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) in the hepatocytes of ovariectomized rats to explore its mechanism of improving insulin resistance. Methods Six-week SD female rats were randomly divided into three groups: sham operation group (Sham group), operation group (OVX group) and estradiol valerate group (E2 group) Aqueous solution (1 mg / kg), while the other groups were given the corresponding volume of distilled water, continuous administration for 12 weeks. Glucose oxidase method was used to measure the blood glucose. The expression of IRS-1 and IRS-2 mRNA in hepatocytes was detected by real-time fluorescence quantitative PCR. The expression of IRS-1 and IRS-2 protein in hepatocytes was detected by immunohistochemistry. Results The body weight, liver weight and visceral fat index (KITT) of OVX rats were significantly higher than that of Sham rats, but the KITT of glucose utilization was significantly lower than that of Sham rats (P <0.05). Compared with OVX rats, The body weight, liver weight and visceral fat index decreased significantly, while the glucose utilization constants increased significantly (P <0.05). The results of immunohistochemistry showed that the number of IRS-1 and IRS-2 positive cells and the staining degree Compared with Sham group, the number of IRS-2 positive cells and the staining degree of hepatic tissue were significantly improved after estrogen replacement therapy, but IRS-1 showed no significant improvement. The expression of IRS-1 and IRS-2 mRNA in OVX rats significantly increased Lower than Sham group, while the expression of IRS-1 and IRS-2 mRNA in E_2 group was significantly higher than that in OVX group (P <0.05). Conclusion Estrogen can up-regulate the expression of IRS-1 and IRS-2 in hepatocytes of ovariectomized rats and further improve insulin resistance.