宫内生长受限大鼠肝脏糖异生酶的表达增加与胰岛素抵抗  

Increased expression of gluconeogenic enzymes in the liver of IUGR rats and subsequent insulin resistance

作　　者：刘晓梅 卢岩[1] 潘莉莉[2] 李书琴[1] 

机构地区：[1]中国医科大学盛京医院实验中心,辽宁沈阳110004 [2]中国医科大学盛京医院检验科,辽宁沈阳110004

出　　处：《中国当代儿科杂志》2008年第2期216-220,共5页Chinese Journal of Contemporary Pediatrics

基　　金：辽宁省自然科学基金资助项目(9910500709)

摘　　要：目的宫内生长受限(IUGR)和成年胰岛素抵抗密切相关,但其发生机制不清楚,该研究通过检测IUGR子鼠肝脏中糖异生关键酶及可促进糖异生的转录因子的表达,探讨IUGR个体发生胰岛素抵抗的分子机制。方法通过孕期全程蛋白质营养不良方法建立大鼠IUGR模型,采用逆转录-聚合酶链反应(RT-PCR)和Western blot技术检测IUGR子鼠幼年和成年肝脏中PGC-1α mRNA和蛋白表达变化,同时检测磷酸烯醇丙酮酸羧激酶(PEPCK)和葡萄糖6-磷酸酶(G6-P酶)的mRNA表达变化。结果①IUGR组子鼠平均出生体重4.97±0.83g明显低于正常对照组6.54±0.52g(P<0.01),4周时IUGR组平均体重达到对照组平均水平,8周时IUGR组体重为152.03±13.57g超过正常对照组的136.05±12.24g(P<0.05);②IUGR子鼠幼年(3周)空腹血糖和胰岛素水平与对照组没有差异,成年(8周)后IUGR子鼠出现高胰岛素血症(P<0.01),胰岛素抵抗指数(IRI)增高(P<0.05);③与对照组相比,IUGR组3周和8周龄子鼠肝脏PGC-1α mRNA和蛋白表达明显增高(P<0.05);同时肝脏PEPCK和G6-P酶的mRNA水平也明显高于对照组(P<0.01)。结论IUGR鼠自幼年至成年肝脏中糖异生的关键调控因子PGC-1α的mRNA和蛋白表达增加,诱导糖异生关键酶的表达,可能增加肝脏糖异生,促进胰岛素抵抗发生。Objective Intrauterine growth retardation （IUGR） is associated with insulin resistance in later life but the mechanism remains unclear. To explore the molecular mechanism of insulin resistance, we determined the expression of gluconeogenic enzymes as well as the expression of transcription factor which promotes gluconeogenesis in the liver of IUGR rats. Methods Rat model of IUGR was established by maternal protein-malnutrition. Hepatic mRNA levels of the key enzymes for gluconeogenesis, PEPCK and G6Pase, and of peroxisome proliferator-activated receptor-.ycoactivator （PGC） - lα were measured by RT - PCR in male IUGR pup rats at 3 and 8 weeks of their lives. Hepatic PGC-lα protein levels were determined by Western blot. Results The average birth weights of the IUGR group （4.97 ± 0.83 g） were significantly lower than normal controls （6.54 ± 0.52 g） （ P 〈 0.01 ）. Until to 4 weeks of age, the weights of the IUGR rats increased to the control level and were higher than normal controls at 8 weeks of age （ P 〈 0.05 ）. There were no significant differences in blood glucose and insulin concentrations between the IUGR rats and normal controls at 3 weeks of＇age. By 8 weeks of age, the IUGR rats showed high insulin concentrations （P 〈0.01 ） and high insulin resistance index （P 〈0.05 ） compared with the controls. Hepatic PGC-1 α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase in IUGR rats significantly increased at 3 and 8 weeks compared with controls. Conclusions An increased PGC-1 α expression may contribute to increased mRNA levels of PEPCK and G6Pase, and thus induce the development of insulin resistance in later life in IUGR rats.

关 键 词：宫内生长受限 胰岛素抵抗 糖异生 大鼠 

分 类 号：R714.5[医药卫生—妇产科学] R587.1[医药卫生—临床医学]