PTEN基因在宫内发育迟缓大鼠肝脏胰岛素敏感性变化中的作用

Effect of PTEN Gene in Change of Insulin Sensitivity in Intrauterine Growth Retardation Rats

目的通过检测PTEN基因在宫内发育迟缓(IUGR)大鼠肝脏中的表达,探讨PTEN基因在IUGR致胰岛素抵抗(IR)中的意义。方法通过孕期低蛋白饮食法建立大鼠IUGR模型,检测90 d雄性IUGR大鼠胰岛素敏感性,采用反转录(RT)-PCR技术检测90 dIUGR组及对照组仔鼠肝脏PTEN基因mRNA表达水平,Western blot检测肝脏组织中丝氨酸/苏氨酸激酶(AKT)蛋白及磷酸化AKT蛋白表达水平。采用SPSS 13.0软件进行统计学处理。结果与对照组比较,IUGR雄性仔鼠平均出生体质量显著降低(t=14.73,P<0.05),空腹血糖显著升高(t=-3.11,P=0.011),空腹胰岛素显著升高(t=-5.01,P=0.001),胰岛素抵抗指数显著升高(t=-3.06,P=0.013),胰岛素敏感指数显著降低(t=2.80,P=0.019),PTEN基因mRNA表达显著升高(t=-2.40,P=0.04),AKT蛋白表达虽然无统计学差异,但磷酸化AKT蛋白表达显著下降(t=3.02,P=0.01),PTEN与胰岛素抵抗指数呈正相关(r=0.928,P<0.05),与磷酸化AKT的表达呈负相关(r=-0.411,P<0.05)。结论 PTEN可能是IUGR致IR的重要调节分子之一。

Objective To explore the effect of PTEN gene in the change of insulin sensitivity in intrauterine growth retardation （IUGR） rats. Methods IUGR model of rat was established through low protein diet during pregnancy. The insulin sensitivity was analyzed in 90 - day male IUGR rats, and PTEN mRNA expression was detected in the liver of IUGR rats and control groups by reverse transcription - PCR tech-nology, and ser-ine threonine kinase （AKT） and phosphorylation （P）AKT expression were detected in the liver of IUGR rats in the both groups by Western blot technology. SPSS 13.0 software was used to analyze the data. Results The average birth weight of IUGR male rats was significantly lower than that of the control offsprings （ t = 14.73, P 〈 0.05 ）, the fasting plasma glucose of IUGR male rats was significantly higher than that of the control offsprings （ t = - 3.11, P = 0.011 ）, the fasting serum insulin of IUGR male rats was significantly higher than that of the control offsprings （ t = - 5.01, P = 0. 001 ）, the insulin resistance index of IUGR male rats was significantly higher than that of the control offsprings （ t = - 3.06, P =0. 013 ）, the insulin sensitivity index of IUGR male rats was significantly lower than that of the control off- springs（ t = 2. 80, P = 0. 019 ）. PTEN mRNA expression in the IUGR offsprings was significantly lower than that of the control offsprings （t = -2.04,P =0.04）, AKT expression in the IUGR offsprings had no significant difference compared with that of the control offsprings, but PAKT expression in the IUGR offsprings was significantly higher than that of the control offsprings （ t = 3.02, P = 0.01 ）. PTEN mRNA expres-sion level was significantly positively correlated with insulin sensitivity （ r = 0. 928,P 〈 0.05 ） , and PAKT level（ r=-0.411, P 〈 0.05 ）. Con-clusion PTEN may be one of the important regulatory molecules for insulin resistance induced by IUGR.