子宫腺肌病在位/异位内膜Toll样受体表达与炎症病理相关性的研究

The Expression of Toll-like Receptors in Eutopic and Ectopic Endometrium and Its Implication in the Inflammatory Pathogenesis of Adenomyosis

目的:检测子宫腺肌病在位/异位内膜Toll样受体(Toll-like receptors,TLRs)表达,探讨TLRs表达与组织炎症病理的相关性。方法:标本选自同济大学附属杨浦医院收治的子宫腺肌病手术患者24例,分别取在位内膜(eutopic endometrium,EU)、异位内膜(ectopic endometrium,EC),并以正常子宫内膜(control endometrium,CE)为对照。检测CE、EU、EC组中TLRs mRNA及蛋白表达,同时检测白细胞介素(IL)-6、IL-8 mRNA表达。结果:逆转录聚合酶链反应(RT-PCR)检测显示:IL-6、IL-8 mRNA在EC、EU组中表达均高于CE组(P<0.01),且EC组高于EU组(P<0.01)。TLR1~6、8、9 mRNA在EC、EU组中表达高于CE组(P<0.05),除外TLR2,其余TLRs在EC组中表达高于EU组(P<0.01)。TLR7 mRNA在EU组中表达高于CE组(P<0.05),而EC组与CE组、EU组与EC组之间差异无统计学意义。蛋白质印迹(Western blot)检测显示:TLR1、4~6、8、9在EC、EU组中表达高于CE组(P<0.01),且EC组高于EU组(P<0.01)。TLR2在EC组中表达高于CE组(P<0.05),而EU组与CE组、EU组与EC组之间差异无统计学意义。TLR3、7在EC组中表达高于EU组及CE组(P<0.05),而EU组与CE组之间差异无统计学意义。Pearson相关性分析显示,子宫腺肌病EU、EC组TLRs mRNA与IL-6、IL-8均呈正相关;其中TLR2、4、5、9与IL-6、IL-8均呈正相关(P<0.05)。结论:子宫腺肌病病灶处于炎症病理状态,腺肌病EU、EC组TLRs整体呈高表达,并与IL-6、IL-8具有良好的相关性,提示TLRs信号介导免疫炎性体系可能涉及子宫腺肌病炎症病理形成及发展。

Objective：To investigate the expression profiles of Toll-like receptors（TLRs） in eutopic endometrium（EU）and ectopic endometrium（EC） and its implication in the inflammatory pathogenesis of adenomyosis. Methods ：A total of 24 adenomyosis patients who underwent laparoscopy were recruited in this study. The mRNA and protein expressions of TLRs, and the mRNA expression of IL-6 and IL-8 in EU and EC of adenomyosis patients, and the control endometrium without adenomyosis（CE） from healthy women were detected. Results ：The mRNA expression of IL-6, IL-8 in EU was significantly higher than that in CE, and was the highest in EC（P 〈0.01）. The mRNA expression of TLR1-6, 8, 9 in EU was significantly higher than that in CE（P 〈0.05）, and were the highest in EC except TLR2（P 〈0.01）. The mRNA expression of TLR7 in EU was significantly higher than that in CE（P 〈0.05）, but there was no significant difference in TLR7 expression between EC vs. CE,EU vs. EC. The protein expression of TLR1, 4-6, 8, 9 in EU was significantly higher than that in CE, and was the highest in EC（P 〈0.01）. The protein expression of TLR2 in EC was significantly higher than that in CE（P 〈0.05）, but there was no significant difference between EU vs. CE, EU vs. EC. The protein expression of TLR3, 7 in EC was significantly higher than that in EU and CE（ P 〈0. 05）, but there was no significant difference between EU vs. CE. Pearson correlation analysis showed that the expression of TLR2, 4, 5 and 9 in EU and EC was positively correlated with that of IL-6 and IL-8（P 〈0.05）. Conclusions：Our results showed that adenomyosis was a state of inflammatory pathology. High expression of TLRs in EU and EC were positively correlated with IL-6 and IL-8, which may be involved in the inflammatory pathogenesis of adenomyosis.