妊娠期糖尿病产妇胎盘组织中TLR4/MyD88/NF-κB的表达及其与胰岛素抵抗的相关性

Expression of TLR4/MyD88/NF-κB in placenta of pregnant women with gestational diabetes mellitus and its correlation with insulin resistance

目的 探讨妊娠期糖尿病(GDM)产妇胎盘组织中Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子-κB(NF-κB)的表达及TLR4与胰岛素抵抗(IR)的相关性。方法 选择如皋市人民医院2017年12月至2018年12月收治的32例GDM患者为GDM组,同期30例正常孕妇为对照组,测定其分娩前外周血中IR相关指标水平,采用实时定量PCR和免疫组化法测定两组产后胎盘组织中TLR4、MyD88、NF-κB mRNA和蛋白的表达水平。采用Spearman秩相关分析GDM产妇胎盘组织中TLR4表达水平与IR的相关关系。结果 GDM组分娩前外周血中FBG、FINS、HOMA-IR水平均明显高于对照组(P<0.01),两组HOMA-β水平比较差异无统计学意义(P>0.05)。GDM组产妇胎盘母体面和胎盘胎儿面TLR4、MyD88和NF-κB蛋白表达水平及mRNA相对表达量均显著高于对照组(P<0.05)。Spearman秩相关分析发现,GDM组胎盘组织母体面及胎儿面TLR4的蛋白表达水平与HOMA-IR呈正相关(r=0.596,P<0.01;r=0.326,P<0.01)。结论 TLR4、MyD88、NF-κB在GDM产妇胎盘组织中表达增高,且TLR4蛋白表达水平与IR程度直接相关。

Objective To investigate the expressions of Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88) and NF-κB in placental tissues of women with gestational diabetes mellitus(GDM) and the relationship between TLR4 and insulin resistance(IR).Methods Thirty-two patients with GDM admitted to Rugao People′s Hospital from December 2017 to December 2018 were selected as GDM group,and 30 normal pregnant women were served as control group at the same time.The levels of IR related indices in the peripheral blood were measured before delivery,and the mRNA and protein expressions of TLR4/MyD88/NF-κB in placental tissue were determined by real-time quantitative PCR and immunohistochemistry in two groups.Spearman rank correlation analysis was used to determine the relationship between TLR4 expression level and IR in GDM women.Results The levels of fasting blood glucose(FBG),fasting insulin(FINS) and Homeostasis model assessment-insulin resistance(HOMA-IR) index in GDM group were significantly higher than those in control group(P<0.01),but HOMA-β levels were similar between two groups(P>0.05).The relative mRNA expressions and protein levels of TLR4/MyD88/NF-κB in maternal and fetal surfaces of the placenta in GDM group were significantly higher than those in control group(P<0.05).Spearman test showed that the expression level of TLR4 in maternal and fetal surfaces of placenta was positively correlated with HOMA-IR in GDM group(r=0.596,P<0.01;r=0.326,P<0.01).Conclusion The expression of TLR4/MyD88/NF-κB is increased in placenta of GDM women,and the protein expression level of TLR4 is directly related to the degree of IR.