胰岛素受体底物在宫内发育迟缓大鼠肝脏组织中的表达

Expression of Insulin Receptor Substrates in Liver of Rats with Intrauterine Growth Retardation

目的研究胰岛素受体底物1(IRS-1)和胰岛素受体底物2(IRS-2)在宫内发育迟缓(IUGR)大鼠出生0周、3周和8周时肝脏组织中的表达,探讨IUGR个体易患代谢综合征(MS)的分子机制。方法采用母孕期低蛋白饮食法建立IUGR大鼠模型,应用反转录(RT)-PCR技术检测仔鼠在出生0周、3周、8周肝脏组织中IRS-1、IRS-2 mRNA水平,凝胶电泳条带用成像系统照相定量分析结果,分别计算PCR产物条带与β-actin条带吸光度值的比值,作为目的基因相对表达量。采用Western blot杂交检测仔鼠在出生0周、3周、8周肝脏组织IRS-1蛋白、IRS-2蛋白的水平表达。母孕期得到正常饮食的仔鼠作为对照组。结果 IUGR鼠出生时体质量显著低于对照组,出生后出现生长追赶,至8周时IUGR组体质量超过对照组;IUGR组0周、3周、8周时其肝脏组织IRS-2 mRNA和蛋白表达水平均显著低于对照组(Pa<0.05,0.01),肝脏组织IRS-1 mRNA和蛋白表达水平与对照组比较差异无统计学意义(Pa>0.05)。结论 IUGR大鼠0周、3周和8周肝脏组织中IRS-2 mRNA和蛋白水平显著下降,可能是IUGR个体易患MS的分子机制之一。

Objective To analyze the expressions of insulin receptor substrate-1（IRS-1） and insulin receptor substrate-2（IRS-2） in the liver of rats with intrauterine growth retardation（IUGR）,and to investigate the mechanism of insulin resistance development. Methods IUGR rat models were prepared by protein malnutrition during pregnancy.The liver samples of the IUGR pups were obtained at birth,and 3 weeks and 8 weeks of age.The expressions of IRS-1 and IRS-2 mRNA were ascertained by reverse transcriptase-PCR.Western blot was used to measure the protein expressions of IRS-1,IRS-2.The rat pups born from the mother rats that received normal diet during pregnancy severed as the control group. Results The expression levels of IRS-2 mRNA and protein in the liver of the IUGR group were significantly lower than those in the control group at different age points（Pa0.05,0.01）.There was no significant difference in the expression levels of IRS-1 mRNA and protein in the liver between the IUGR and the control group（Pa0.05）. Conclusions The IRS-2 expression levels in IUGR rats decrease significantly at birth,and 3 weeks and 8 weeks of age.This might be one of the molecular mechanisms for the development of metabolic syndrome in later life in IUGR individuals.