目的　研究胰岛素受体底物(IRS)-1和IRS-2在生长追赶宫内发育迟缓新生大鼠脂肪细胞中的时序性表达及其与胰岛素抵抗的关联。方法　通过母鼠孕期全程饲料限制建立宫内发育迟缓模型，相对增加哺乳期子鼠营养摄入实现生长追赶。于4周龄时心脏采血测定空腹血糖、胰岛素和三酰甘油，计算胰岛素抵抗指数。测定1、3、5、7周龄SD大鼠的成熟脂肪细胞及前脂肪细胞分化的成熟脂肪细胞的IRS-1和IRS-2 mRNA以及蛋白水平的变化。结果　生长追赶的宫内发育迟缓新生大鼠原代培养的成熟脂肪细胞IRS-1和IRS-2 mRNA表达分别于生后第5周和第7周显著下调，差异有统计学意义(P<0.05)；前脂肪细胞分化的成熟脂肪细胞IRS-1和IRS-2 mRNA表达均于生后第5周显著下调，差异有统计学意义(P<0.05)；两种成熟脂肪细胞IRS-1和IRS-2蛋白水平均于生后第1周开始显著下调，差异有统计学意义(P<0.05)。结论　生长追赶的宫内发育迟缓新生大鼠脂肪细胞IRS-1和IRS-2的基因表达发生相对下调，可能与其生后远期的胰岛素抵抗密切相关。

Objective　To investigate the expressions of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) in adipocytes during catch-up growth in neonatal rats with intrauterine growth restriction (IUGR) and their correlations with the insulin resistance. Methods Sprague-Dawley rats (clean grade) were randomly divided into control group and food-restricted group after fertilization. Food-restricted group were received about 30% of food amount consumed in control group every day through the whole pregnant period to establish IUGR animal model, and were fed increased amount of breastmilk from postnatal day 1 to 21 to establish the period of catch-up growth in IUGR animal model (IUGR-CG). Fasting serum glucose, insulin and triglyceride were measured in blood from heart ventricles of 4-week old SD rats and insulin resistance index was calculated. Pre-adipocytes and mature adipocytes were obtained from SD rats at different age (1-week, 3-week, 5-week and 7-week old) and the former were induced to differentiate toward mature adipocytes. The levels of IRS-1, IRS-2 in the two kinds of mature adipocytes were detected by Real-Time PCR and Western blot. Results The expression levels of IRS-1, IRS-2 mRNA in mature adipocytes of IUGR-CG rats were significantly lower than those of IUGR rats at 5-weeks and 7-weeks old (P<0.05) while the expression levels of IRS-1, IRS-2 mRNA in differentiated adipocytes of IUGR-CG rats were significantly lower than those of IUGR rats at 5-weeks old (P<0.05). The expression levels of IRS-1, IRS-2 protein in two kinds of adipocytes (mature and differentiated adipocytes) of IUGR-CG rats were significantly lower than those of IUGR rats from postpartum week 1 through 7 (P<0.05). Conclusions IRS-1 and IRS-2 expression levels are downregulated in adipocytes during catch-up growth of IUGR rats, which may be closely related with insulin resistance.