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目的探讨生后无生长追赶的出生低体重(NCU-SGA)幼鼠的胰岛素抵抗对生长激素(GH)抵抗的影响及其受体后信号转导机制。方法以母鼠孕期限制饮食法建立雄性 NCU-SGA 模型研究:(1)GH 和胰岛素抵抗的关系:测定4周龄时24 h 尿 GH 排泄率(24 h U-GH),血胰岛素样生长因子(IGF)-1、空腹胰岛素(FINS)、血糖以及肝组织 IGF-1 mRNA 和 STAT5信号表达;(2)胰岛素抵抗对生长轴的影响:3周龄时注射 PI3K 阻断剂1周后(设溶剂对照组),测定大鼠体格生长,血 IGF-1、FINS 水平及肝 IGF-1 mRNA 和 STAT5信号表达。结果 (1)NCU-SGA 鼠血清 IGF-1浓度、肝 IGF-1mRNA 表达以及磷酸化与总 STAT 蛋白表达水平的比率均显著低于健康对照组(C 组),分别为(248±58)ng/ml,(6.1±0.3)拷贝和(61±22)%;C 组为(383±62)ng/ml,(6.6±0.4)拷贝和(91±29)%(均 P<0.01);NCU-SGA 组与 C 组的24 h U-GH 差异无统计学意义(P>0.05);NCU-SGA 组FINS 及空腹血糖为(24.7±9.6)mU/ml 和(5.4±0.3)mmol/L 显著高于 C 组的(9.8±2.8)mmol/L和(4.5±1.7)mmol/L(均 P<0.05)。24 h U-GH 与 FINS 显著正相关(r=0.680,P=0.000)。(2)PI3K 阻断后 NCU-SGA 鼠胰岛素抵抗加重,体重下降,血清 IGF-1及肝 IGF-1 mRNA 为(218±60)ng/ml 及(6.1±0.3)拷贝,显著低于溶剂对照组的(286±45)ng/ml 及(6.3±0.3)拷贝,均 P<0.05。但两组间肝组织总的及磷酸化 STAT5信号表达水平差异无统计学意义。结论 NCU-SGA 幼鼠的胰岛素抵抗与 GH 抵抗密切相关。生后无追赶与 GH 受体后 JAK2-STAT5通路受损所致的 GH 抵抗有关。胰岛素抵抗可能经非 STAT5依赖途径加重了 GH 抵抗及生长障碍。
Objective To investigate the effect of insulin resistance on growth hormone (GH) resistance in neonatal low birth weight (NCU-SGA) rats and its post-receptor signal transduction mechanism. METHODS: The male NCU-SGA model was established with diet restriction method during pregnancy. (1) The relationship between GH and insulin resistance: The 24 h urinary GH excretion rate (24 h U-GH), insulin-like growth factor (IGF-1), fasting insulin (FINS), blood glucose and the expression of IGF-1 mRNA and STAT5 in liver tissue. (2) The effect of insulin resistance on the growth axis: After 3 weeks of PI3K blockade Solvent control group). The body growth, serum IGF-1, FINS and the expression of IGF-1 mRNA and STAT5 in liver were measured. Results (1) The serum IGF-1 concentration, IGF-1 mRNA expression and the ratio of phosphorylation to total STAT protein in NCU-SGA rats were significantly lower than those in healthy controls (C ± C) / (6.1 ± 0.3) copies and (61 ± 22)% in group C, (383 ± 62) ng / ml in group C, 6.6 ± 0.4 copies in control group and 91 ± 29% in control group There was no significant difference in 24 h U-GH between -SGA group and C group (P> 0.05). FINS and fasting blood glucose in NCU-SGA group were (24.7 ± 9.6) mU / ml and (5.4 ± 0.3) mmol / L (9.8 ± 2.8) mmol / L and (4.5 ± 1.7) mmol / L respectively in group C (all P <0.05). 24 h U-GH was significantly and positively correlated with FINS (r = 0.680, P = 0.000). (2) The insulin resistance and weight loss of NCU-SGA mice after PI3K block were significantly lower than that of the solvent control group (218 ± 60 ng / ml and 6.1 ± 0.3 copies of IGF-1 and IGF-1 mRNA) (286 ± 45) ng / ml and (6.3 ± 0.3) copies, all P <0.05. However, there was no significant difference in total and phosphorylated STAT5 expression between the two groups. Conclusion Insulin resistance in neonatal rats with NCU-SGA is closely related to GH resistance. No chase after birth related to GH resistance induced by impaired JAK2-STAT5 pathway after GH receptor. Insulin resistance may aggravate GH resistance and growth disorders via a non-STAT5-dependent pathway.