性激素结合球蛋白、胰岛素信号转导蛋白和葡萄糖转运蛋白在妊娠期糖尿病胎盘组织中的表达及相关性分析

Expression and Correlation of Sex Hormone-binding Globulin,Insulin Signal Transduction and Glucose Transporter Proteins in the Gestational Diabetes Mellitus Placental Tissue

目的研究妊娠期糖尿病(GDM)孕妇胎盘组织中性激素结合球蛋白(SHBG)、胰岛素信号转导蛋白及葡萄糖转运蛋白表达,探讨其在GDM发病过程中的作用。方法收集足月妊娠且非肥胖(BMI<25 kg/m2)GDM孕妇(GDM组)和同期糖代谢正常(正常组)孕妇胎盘组织各10例,应用Western blotting、实时PCR方法检测2组胎盘组织中SHBG和胰岛素信号转导蛋白(IRS-1、ISR-2、PI3K p85α)和葡萄糖转运蛋白(GLUT-1、GLUT-3、GLUT-4)的表达,各指标进行直线回归依存关系分析。结果与正常组比较,GDM组胎盘组织中SHBG m RNA、蛋白表达降低(P<0.05);IRS-1蛋白、IRS-2 m RNA表达降低(P<0.05);PI3K p85α和GLUT-1蛋白及其m RNA表达无统计学差异(P>0.05);GLUT-3蛋白,GLUT-4 m RNA、蛋白表达降低(P<0.05)。直线回归分析结果显示SHBG m RNA与IRS-2 m RNA、PI3K p85αm RNA、GLUT-4 m RNA的表达呈正相关(均P<0.05);IRS-2 m RNA和GLUT-4 m RNA的表达呈正相关(P<0.01);IRS-1 m RNA和PI3K p85αm RNA、GLUT-3 m RNA的表达呈负相关(P<0.05);IRS-2m RNA和GLUT-1 m RNA的表达正相关(P<0.01)。结论 GDM孕妇胎盘中胰岛素信号转导和葡萄糖转运蛋白存在异常,SHBG可能参与胰岛素信号通路的调节,GDM时胎盘滋养细胞合成和分泌SHBG减少,引起胰岛素信号转导通路相关蛋白表达降低,从而导致胰岛素抵抗及GDM的发生。

Objective To study the expression of sex hormone-binding globulin （SHBG）, insulin signaling pathway and glucose transporter in placenta of pregnant women with gestational diabetes mellitus （GDM）, and to explore its role in the pathogenesis of GDM. Methods A total of 10 full-term and non-obese （BMI〈25 kg/m2） pregnancy women diagnosed with GDM and 10 normal pregnant cases were recruited for the study. Placental tissues were collected respectively. The expression of protein and mRNA of SHBG and insulin signal transduction （IRS-1, ISR-2, PI3K p85α） and glucose transporter proteins （GLUT-1, GLUT-3, GLUT-4） in placental tissue were detected by real-time PCR and Western blotting. Pearson and linear regression analysis were used to evaluate the correlation among the related indicators. Results In the placental tissue of nonobese women, there existed a decrease （P 〈 0.05） in the expression of protein and mRNA of SHBG with a concurrent a decrease （P 〈 0.05） in the expression of protein and mRNA of GLUT-4 in GDM women compared with normal controls. Furthermore, a decrease （P 〈 0.05 ） of GLUT-3 and IRS-1 protein expression with lower （P 〈 0.05） IRS-2 mRNA expression was also observed in placental tissue from GDM patients. No changes were found in PI3K p85αand GLUT- 1 at both protein and mRNA levels （P 〉 0.05）. Results of linear correlation analysis showed that there were positive correlations between SHBG mRNA and IRS-2 mRNA （P 〈 0.05 ）, SHBG mRNA and PI3K p85α mRNA （P 〈 0.05 ）, and SHBG mRNA and GLUT-4 mRNA （P 〈 0.05 ）. There was also a remarkable positive correlation between IBS-2 mRNA and GLUT-4 mRNA （P 〈 0.01 ）. There existed negative correlations between IRS-1 mRNA and PI3K p85α mRNA （ P 〈 0.05 ）, and IRS-1 mRNA and GLUT-3 mRNA （ P 〈 0.05 ）. There existed a remarkable positive correlation between IRS-2 mRNA and GLUT-1 mRNA （P 〈 0.01 ）. Conclusion The defective receptors of insulin signaling pathway are present in GDM placental tissue. Decreased expression of SHBG may be involved in the regulation insulin signaling, leading to a concomitant decrease expression of relevant insulin signaling components in placental tissue, implying insulin resistance and developing GDM finally.