11β-HSD1和11β-HSD2在妊娠期糖尿病患者胎盘组织中的差异表达及临床意义

Differential expression of placental tissue 11β-HSD1 and 11β-HSD2 in patients with gestational diabetes mellitus

目的研究妊娠糖尿病患者胎盘组织中11β-羟类固醇脱氢酶(11β-HSD1)和11β-HSD2基因和蛋白表达的变化及意义。方法选择妊娠期糖尿病(GDM)和糖耐量正常孕妇(NGT)各30例,化学发光法测定皮质醇、胰岛素的水平,免疫组织化学法检测11β-HSD1和11β-HSD2在胎盘的表达部位,分别运用荧光定量PCR(real time PCR)和Western blot法测试11β-HSD1和11β-HSD2基因和蛋白水平的差异表达。结果与NGT组相比,GDM组空腹胰岛素、HOMA-IR、胰岛素分泌指数、母血皮质醇水平明显增高(P<0.05),而空腹血糖、胎儿脐血皮质醇则差异无统计学意义(P>0.05)。1β-HSD1和11β-HSD2均在胎盘中有表达,表达部位及水平不同。real time-PCR和Western blot检测结果提示GDM组胎盘11β-HSD1mRNA和蛋白的表达明显低于NGT组(P<0.05),11β-HSD2mRNA明显高于NGT组(P<0.05),而蛋白水平差异无统计学意义(P>0.05)。结论妊娠期糖尿病胎盘组织11β-HSD1和11β-HSD2差异表达调整免除母体不佳的妊娠环境将会给胎儿造成的长远伤害。

Objective To study the changes and significance of 11β-HSD1 and 11β-HSD2 gene and protein expression in placenta of patients with gestational diabetes mellitus.Methods Thirty pregnant women with gestational diabetes mellitus(GDM)and normal glucose tolerance(NGT)were selected.Chemiluminescence was used to determine the serum cortisol,neonatal cord blood cortisol and fasting insulin ect.Immunohistochemistry was used to detect the expression location of 11β-HSD1 and 11β-HSD2 in the placenta.The differential expression of 11β-HSD1 and 11β-HSD2 genes and proteins were detected by real-time PCR and Western blot.Results Compared with NGT group,fasting insulin,HOMA-IR,insulin secretion index and maternal serum cortisol level were significantly increased in GDM group[(19.95±1.05)mU/L vs.(12.93±1.50)mU/L,4.54±0.67 vs.2.87±0.43,80.55±6.18 vs.53.15±5.58,(1 110.00±40.91)nmol/Lvs.(934.1±45.92)nmol/L,P<0.05)],but there were no significant differences were found in fasting blood glucose and cord blood cortisol(P>0.05).The distribution of 11β-HSD1 in the placenta was distributed in the outer layer of villous syncytiotrophoblast,villous interstitial and dry villi.The expression of 11β-HSD2 was concentrated in the outer layer of villous syncytiotrophoblast.Real time-PCR and Western blot results showed that the expression of11β-HSD1 mRNA and protein in placenta of GDM group was significantly lower than that of NGT group(0.56±0.09 vs.1.36±0.36,0.27±0.07 vs.1.00±0.01,P<0.05),11β-HSD2 mRNA was significantly higher than NGT group(5.17±1.02 and1.21±0.34 respectively,P<0.05),but no significant difference was found in protein level(P>0.05).Conclusion The differential expression of 11β-HSD1 and 11β-HSD2 in placenta of gestational diabetes mellitus can avoid the maternal poor pregnancy environment,but will cause long-term harm to the fetus.