目的:研究宫腔粘连(IUAs)组织中Toll样受体4(TLR4)/核因子κB(NF-κB)通路功能改变与细胞因子分泌、胶原代谢特征的相关性。方法:选择在我院就诊的IUAs患者作为IUAs组,同期因不孕行宫腔镜检查且经病理证实子宫内膜正常的患者作为对照组。测定IUAs组粘连组织及对照组正常子宫内膜组织中TLR4/NF-κB通路分子、胶原代谢基因的表达水平及细胞因子、胶原代谢标志分子的含量。结果:IUAs粘连组织中TLR4、NF-κB、解整合素金属蛋白酶 15(ADAM15)、ADAM17、基质金属蛋白酶9(MMP9)、纤溶酶原激活剂抑制剂-1(PAI-1)的mRNA表达量以及转化生长因子-β1(TGF-β1)、Smad2/3、胰岛素样生长因子-1(IGF-1)、IGF-1受体(IGF-1R)、碱性成纤维细胞生长因子(bFGF)、骨膜蛋白成骨细胞特异性因子2(Postn)、I型胶原(Col-I)、肌动蛋白-α(α-SMA)的含量明显高于对照组,尿激酶纤溶酶原激活剂(uPA)的mRNA表达量明显低于对照组；TLR4、NF-κB的mRNA表达量与TGF-β1、Smad2/3、IGF-1、IGF-1R、bFGF、Postn、Col-I、α-SMA、ADAM15、ADAM17、MMP9、PAI-1呈正相关,与uPA呈负相关。结论:IUAs组织TLR4/NF-κB通路的过度激活与细胞因子分泌及胶原代谢异常有关。

Objective: To study the correlation of the changes of Toll-like receptor 4 (TLR4) / nuclear factor κB (NF-κB) pathway function in intrauterine adhesion (IUAs) tissue with the characteristics of cytokine secretion and collagen metabolism. Methods: The patients with IUAs who were treated in our hospital between February 2015 and March 2018 were selected as the IUAs group, and the patients who underwent hysteroscopy due to infertility and were pathologically confirmed to have normal endometrium during the same period were selected as the control group. The expression levels of TLR4/NF-κB pathway molecules and collagen metabolism genes as well as the contents of cytokines and collagen metabolism markers in the adhesion tissues of IUAs group and the normal endometrial tissue of control group were measured. Results: TLR4, NF-κB, a disintegrin and metalloproteinase 15 (ADAM15), ADAM17, matrix metalloproteinase 9 (MMP9) and plasminogen activator inhibitor 1 (PAI-1) mRNA expression as well as transforming growth factor-β1 (TGF-β1), Smad2/3, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), basic fibroblast growth factor (bFGF), periostin/osteoblast-specific factor 2 (Postn), type I collagen (Col-I) and actin-α (α-SMA) contents in the adhesion tissues of IUAs group were significantly higher than those of control group while urokinase-type plasminogen activator (uPA) mRNA expression was significantly lower than that of control group (P<0.05); TLR4 and NF-κB mRNA expression were positively correlated with TGF-β1, Smad2/3, IGF-1, IGF-1R, bFGF, Postn, Col-I, α-SMA, ADAM15, ADAM17, MMP9 and PAI-1, and negatively correlated with uPA. Conclusion: The excessive activation of TLR4/NF-κB pathway in IUAs is associated with the cytokine secretion and collagen metabolism abnormalities.

R711

首都医科大学附属北京妇产医院中青年学科骨干培养专项(FCYY201521)