子宫腺肌病EMI微环境变化与TGFβ1的相关性研究

Study on correlation between TGF-β1 and EMI microenvironment in adenomyosis

目的从子宫腺肌病(AM)内膜肌层界面(EMI)微环境变化与转化生长因子β1(TGFβ1)的相关性探索其发生上皮细胞间质转化的可能机制。方法选择2017年3月至2018年3月在三峡大学人民医院行子宫切除的AM患者52例为AM组,收集增生期子宫肌层交界处内膜组织;另选取48例子宫肌瘤患者的增生期非瘤区内膜作为对照组。Western blot检测雌激素核受体(GPER1)、雌激素膜受体(ERα)及炎症微环境因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及TGF-β1表达水平,并分析各因子间的相关性。结果AM组TGF-β1、IL-1β表达水平显著高于对照组(P=0.045、0.032),TNF-α表达水平AM组与对照组间差异无统计学意义(P=0.227)。AM组GPER1表达水平高于对照组,但差异无统计学意义(P=0.510);AM组ERα表达水平显著低于对照组(P=0.006);AM组GPER1/ERα显著高于对照组(P=0.004)。IL-1β、TNF-α与TGF-β1表达水平显著相关(P=0.015、0.004);TNF-α与IL-1β表达水平显著相关(P<0.01)。GPER1与TGF-β1表达水平显著相关(P=0.015)。ERα与TGF-β1表达水平无明显相关性(P=0.195)。结论AM在EMI存在的促炎因子和内分泌紊乱,各信号通路的交互作用共同形成了上皮细胞间质转化的微环境。

Objective To explore the possible mechanism of epithelial mesenchymal transformation of adenomyosis from the correlation between endometrial-myometrial interface(EMI)microenvironment changes of adenomyosis and transforming growth factorβ1(TGF-β1)expression.Methods 52 cases of adenomyosis patients undergoing hysterectomy in the People′s Hospital of Three Gorges University from March 2017 to March 2018 were selected as the AM group to collect endometrial tissue and abnormal endometrial tissue at the junction of myometrium in the proliferative stage.In addition,48 cases of uterine fibroids were selected as the control group.Western blot method was used to detect the expression levels of Gprotein-coupled estrogen receptor-1(GPER1),estrogen receptor(ERα),and inflammatory microenvironmental factors TNF-α,IL-1β,and TGF-β1,in order to analyze the correlation among the factors.Results The expression levels of TGF-β1 and IL-1βin the AM group were significantly higher than those in the control group(P=0.045,0.032),and TNF-αwas not significantly different from the control group(P=0.227).The expression of GPER1 in the AM group was slightly higher than that in the control group,but there was no significant difference(P=0.510).The expression of ER-αin the AM group was significantly lower than that in the control group(P=0.006).GPER1/ER was significantly higher in the AM group than in the control group(P=0.004).The expression of IL-1βwas significantly correlated with TGF-β1(P=0.015).TNF-αwas significantly correlated with TGF-β1 expression(P=0.004).TNF-αwas significantly correlated with IL-1βexpression(P<0.01).GPER1 was significantly correlated with TGF-β1(P=0.015).ERαexpression was not significantly correlated with TGF-β1(P=0.195).Conclusion The pro-inflammatory factors and endocrine disorders existed at the myometrium interface of AM,and the interaction of various signaling pathways together formed the microenvironment of epithelial mesenchymal transformation.