| 杨珊珊,王 慧,刘 燕,户燕姣,马德花.NF-κB与TNF-α在子宫内膜息肉组织中的表达及其临床意义[J].,2025,(18):2881-2889 |
| NF-κB与TNF-α在子宫内膜息肉组织中的表达及其临床意义 |
| Expression of NF-κB and TNF-α in Endometrial Polyps and Their Clinical Significance |
| 投稿时间：2025-05-21 |
| DOI：10.13241/j.cnki.pmb.2025.18.001 |
| 中文关键词: 子宫内膜息肉 NF-κB TNF-α 炎症反应 信号通路 |
| 英文关键词: Endometrial polyp NF-κB TNF-α Inflammatory response Signaling pathway |
| 基金项目:卫生健康发展促进项目（肿瘤科研专项）（BJHA- CRP-001） |
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| 中文摘要: |
| 摘要 目的：探讨核因子κB（NF-κB）与肿瘤坏死因子-α（TNF-α）在子宫内膜息肉组织、息肉旁内膜及正常子宫内膜中的表达差异，分析其与子宫内膜局部炎症反应的相关性，为阐明子宫内膜息肉发病机制提供依据。方法：纳入2023年9月至2024年12月青岛大学附属医院经宫腔镜确诊的子宫内膜息肉患者36例，术中采集息肉组织及距息肉0.5 cm-1 cm处内膜组织（息肉旁组）；另选同期因子宫肌瘤行子宫切除、术后病理证实良性内膜的26例患者作为对照（正常组）。采用免疫组化检测NF-κB与TNF-α蛋白的表达情况，RT-qPCR检测NF-κB及TNF-α mRNA表达水平，Western blot检测其蛋白表达，比较三组间差异。结果：免疫组化结果显示：NF-κB p65 主要定位于细胞质和/或细胞核；TNF-α阳性表达主要位于细胞胞浆和/或细胞膜，表现为棕黄色至棕褐色颗粒。NF-κB蛋白阳性表达率在子宫内膜息肉组织中显著高于息肉旁子宫内膜组织及正常子宫内膜组织（P<0.05），但息肉旁组织与正常内膜组织间差异无统计学意义（P>0.05）。TNF-α蛋白阳性表达率呈梯度变化：子宫内膜息肉组织 > 息肉旁子宫内膜组织 > 正常子宫内膜组织（各组间比较P均<0.05）。实时荧光定量PCR检测显示，NF-κB与TNF-α mRNA在子宫内膜息肉组织中的表达呈显著梯度趋势：NF-κB mRNA：息肉组（7.15±3.15）>息肉旁组（4.38±2.01）>正常组（1.03±0.30），组间差异均显著（均P<0.05）；TNF-α mRNA：息肉组织（17.66±9.25）>息肉旁组织（9.35±5.75）>正常内膜（1.16±0.58），组间差异均具统计学意义（P<0.05）。Western blot蛋白定量分析进一步验证该趋势：NF-κB蛋白：息肉组（0.87±0.11）表达量为正常组（0.39±0.02）的2.23倍（P=0.0007），息肉旁组（0.59±0.07）较正常组升高51 %（P=0.0435）；TNF-α蛋白：息肉组（1.13±0.21）较息肉旁组（0.58±0.03）升高94.8 %（P=0.0036），较正常组（0.19±0.03）升高494.7 %（P=0.0002），单因素方差分析显示组间差异显著（F=43.56，P<0.05）。结论：TNF-α介导的NF-κB信号通路在子宫内膜息肉中异常激活，且在息肉发生部位表达最高，提示局部慢性炎症微环境可能通过持续刺激NF-κB通路促进息肉形成，靶向调控该通路为预防息肉复发提供新策略。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the differential expression of Nuclear Factor Kappa B (NF-κB) and Tumor Necrosis Factor-Alpha (TNF-α) in endometrial polyp tissues, polyp-adjacent endometrium, and normal endometrium, and to analyze their correlation with local inflammatory responses, thereby elucidating the pathogenesis of endometrial polyps. Methods: Thirty-six patients with hysteroscopically confirmed endometrial polyps at Qingdao University Affiliated Hospital (September 2023-December 2024) were enrolled. Polyp tissues and adjacent endometrial tissues (0.5 cm - 1 cm from polyps) were collected during surgery. Twenty-six patients undergoing hysterectomy for uterine fibroids, with pathologically confirmed normal endometrium, served as controls. The expression of NF-κB and TNF-α proteins was assessed using immunohistochemistry (IHC). Real-time quantitative PCR (RT-qPCR) was employed to detect the mRNA expression levels of NF-κB and TNF-α, and Western blot analysis was used to measure their protein expression. Differences among the three groups were compared. Results: Immunohistochemical analysis demonstrated: NF-κB p65 was predominantly localized to the cytoplasm and/or nucleus; TNF-α-positive expression was principally observed in the cytoplasmic compartment and/or cell membrane, manifesting as brown-yellow to brownish granules. The positive expression rate of NF-κB protein was significantly elevated in endometrial polyp tissues compared to both adjacent endometrial tissues and normal endometrial tissues (P<0.05), whereas no statistically significant difference was observed between adjacent and normal endometrial tissues (P>0.05). TNF-α protein expression exhibited a gradient pattern: Endometrial polyp tissues > Adjacent endometrial tissues > Normal endometrial tissues(with all inter-group comparisons demonstrating statistically significant differences, P<0.05). Real-time quantitative PCR analysis revealed a significant gradient trend in the mRNA expression of NF-κB and TNF-α in endometrial polyp tissues: NF-κB mRNA: Polyp group (7.15±3.15) > parapolyp group (4.38±2.01) > normal group (1.03±0.30), with significant intergroup differences (all P<0.05). TNF-α mRNA: Polyp tissue (17.66±9.25) > parapolyp tissue (9.35±5.75) > normal endometrium (1.16±0.58), with statistically significant differences among all groups (all P<0.05). Western blot quantification further confirmed this trend: NF-κB protein: Expression in the polyp group (0.87±0.11) was 2.23-fold higher than in the normal group (0.39±0.02) (P=0.0007), while the parapolyp group (0.59±0.07) showed a 51 % increase compared to the normal group (P=0.0435). TNF-α protein: Expression in the polyp group (1.13±0.21) was elevated by 94.8 % versus the parapolyp group (0.58±0.03, P=0.0036) and by 494.7 % versus the normal group (0.19±0.03, P=0.0002). One-way ANOVA indicated significant intergroup differences (F=43.56, P<0.05). Conclusion: The TNF-α-mediated NF-κB signaling pathway is abnormally activated in endometrial polyps, exhibiting its highest expression at the polyp site. This suggests that the localized chronic inflammatory microenvironment may promote polyp formation through persistent stimulation of the NF-κB pathway. Targeted regulation of this pathway offers a novel strategy for preventing polyp recurrence. |
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