血清TGF-β1、MMP-9和TIMP-1对子宫内膜息肉切除术后发生宫腔粘连的预测价值

摘要/Abstract

摘要： 目的：筛选子宫内膜息肉切除术后发生宫腔粘连的影响因素，并探讨血清转化生长因子β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)和金属蛋白酶抑制因子-1(TIMP-1)水平在预测术后2年内发生宫腔粘连的诊断价值。方法：选择2016年1月至2019年6月在我院实施宫腔镜子宫内膜息肉切除术的患者341例，术后对所有患者均进行2年的随访，期间失访23例。术后2年出现宫腔粘连53例，为宫腔粘连组；未发生宫腔粘连患者265例，为非宫腔粘连组。采用酶联免疫吸附试验测定患者术前的血清TGF-β1、MMP-9和TIMP-1表达水平。通过单因素分析和多因素二元Logistics回归分析筛选出与宫腔镜子宫内膜息肉切除术后发生宫腔粘连相关的危险因素，采用受试者工作曲线(ROC曲线)分析血清TGF-β1、MMP-9和TIMP-1水平在预测子宫内膜息肉切除术后2年内发生宫腔粘连的诊断效能。结果：子宫内膜息肉切除术后2年内发生宫腔粘连与孕次、剖宫产史、刮宫史、内膜增生、盆腔炎史、多发息肉、血清TGF-β1、MMP-9和TIMP-1水平具有相关性(P<0.01)，而与年龄、产次、引产史、宫内节育器史、绝经和体质量指数无相关性(P>0.05)。多因素回归分析发现孕次、盆腔炎史、血清TGF-β1和TIMP-1水平是术后2年内发生宫腔粘连的独立危险因素(P<0.05)，而血清MMP-9水平是术后发生宫腔粘连的保护因子(P<0.05)。轻度粘连组、中度粘连组和重度粘连组患者术前的血清TGF-β1、MMP-9和TIMP-1水平差异均有统计学意义(P<0.01)。血清TGF-β1、MMP-9和TIMP-1水平在预测术后2年内发生宫腔粘连具有较高的联合诊断效能，联合检测的灵敏度为92.5%，特异度为79.6%，曲线下面积为0.932，均优于单个指标TGF-β1(Z=4.752，P<0.01)、MMP-9(Z=4.061，P<0.01)和TIMP-1(Z=3.709，P<0.01)。结论：孕次、盆腔炎史、血清TGF-β1、MMP-9和TIMP-1水平是子宫内膜息肉切除术后2年内发生宫腔粘连的影响因子，血清TGF-β1、MMP-9和TIMP-1水平在预测子宫内膜息肉切除术后2年内发生宫腔粘连具有重要的诊断价值，可为该类患者采取进一步干预措施提供理论依据。

关键词: font-size:medium, ">子宫内膜息肉；宫腔粘连；转化生长因子β1；基质金属蛋白酶-9；金属蛋白酶抑制因子-1

Abstract: Objective：To screen out the risk factors of intrauterine adhesion after endometrial polypectomy， and to investigate the diagnostic value of serum transforming growth factor-β1 (TGF-β1)， matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1)levels in predicting intrauterine adhesion within 2 years after endometrial polypectomy. Methods：341 cases of hysteroscopic surgery for endometrial polyps in our hospital from January 2016 to June 2019 were selected. All the patients were followed up for 2 years after surgery. 23 cases were lost to follow-up. 53 cases occurred intrauterine adhesion within 2 years after surgery(the intrauterine adhesion group)， and 265 casesdidn′t occurre intrauterine adhesion(the intrauterine non adhesion group). The pre-operation serum TGF-β1， MMP-9 and TIMP-1 levels were detected by enzyme-linked immunosorbent assay. The risk factors for intrauterine adhesions after hysteroscopy were screened out by univariate analysis and multivariate Logistics analysis. The diagnostic efficacy of serum TGF-β1， MMP-9 and TIMP-1 levels in predicting intrauterine adhesions within 2 years after endometrial polypectomywere analyzed by receiver operating characteristics (ROC) curve.Results：The occurance of intrauterine adhesion within 2 years after endometrial polypectomy was correlated with pregnancy times， history of cesarean section， curettage， endometrial hyperplasia， pelvic inflammation， multiple polyps， serum TGF-β1， MMP-9 and TIMP-1 levels (P<0.01)， but was not correlated with age， times of labor， history of induced labor， history of IUD， menopause and body mass index (P>0.05). Multivariate analysis showed that pregnancy times， history of pelvic inflammatory， serum TGF-β1 and TIMP-1 levels were independent risk factors for intrauterine adhesion within 2 years after endometrial polypectomy (P<0.05)， while the serum MMP-9 level was a protective factor for postoperative intrauterine adhesion (P<0.05). The preoperative levels of serum TGF-β1， MMP-9 and TIMP-1 in mild adhesion group， moderate adhesion group and severe adhesion group were statistically significant (P<0.01).Serum Levels of TGF-β1， MMP-9 and TIMP-1 have high combined diagnostic efficacy in predicting intrauterine adhesions 2 years after endometrial polypectomy.The sensitivity of combined detection was 92.5%， the specificity was 79.6%， and the area under the curve was 0.932， which was better than single factor， TGF-β1 (Z=4.752， P<0.01)， MMP-9 (Z=4.061， P<0.01) and TIMP-1 (Z=3.709， P<0.01). Conclusion：Pregnancy times， history of pelvic inflammation， serum TGF-β 1， MMP-9 and TIMP-1 levels were the influencing factors of the occurrance of intrauterine adhesion within 2 years after endometrial polypectomy， and serum TGF-β1， MMP-9 and TIMP-1 levels have important diagnostic value in predicting intrauterine adhesion within 2 years after endometrial polypectomy， which can provide a theoretical basis for further intervention in these patients.

Key words: font-size:medium, ">Endometrial polyps； Intrauterine adhesion； Transforming growth factor-β1； Matrix metalloproteinase-9； Tissue inhibitor of metalloproteinase-1

中图分类号:

汪义泳, 杜景云, 管玉宇, 周士华, 余木兰, 顾群, 徐春香, 方婷婷. 血清TGF-β1、MMP-9和TIMP-1对子宫内膜息肉切除术后发生宫腔粘连的预测价值[J]. 中国医药导刊, 2023, 25(1): 61-66.

WANG Yiyong, DU Jingyun, GUAN Yuyu, ZHOU Shihua, YU Mulan, GU Qun, XU Chunxiang, FANG Tingting. Predictive Value of Serum TGF-β1， MMP-9 and TIMP-1 in Intrauterine Adhesion after Endometrial Polypectomy[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2023, 25(1): 61-66.

参考文献

[1]Leung RK， Lin Y， Liu Y. Recent advances in understandings towards pathogenesis and treatment for intrauterine adhesion and disruptive insights from single-cell analysis[J]. Reprod Sci，2021，28(7)：1812-1826.
     [2]Healy MW， Schexnayder B， Connell MT， et al. Intrauterine adhesion prevention after hysteroscopy： a systematic review and meta-analysis[J]. Am J Obstet Gynecol，2016，215(3)：267-275.
     [3]Zhu HY， Ge TX， Pan YB， et al. Advanced role of hippo signaling in endometrial fibrosis： implications for intrauterine adhesion[J]. Chin Med J (Engl)，2017，130(22)：2732-2737.
     [4]Abudukeyoumu A， Li M Q， Xie F. Transforming growth factor-beta1 in intrauterine adhesion[J]. Am J Reprod Immunol，2020，84(2)：e13262.
     [5]Liu X， Wei Y， Bai X， et al. Berberine prevents primary peritoneal adhesion and adhesion reformation by directly inhibiting TIMP-1[J]. Acta Pharm Sin B，2020，10(5)：812-824.
     [6]中华医学会妇产科学分会. 宫腔粘连临床诊疗中国专家共识[J]. 中华妇产科杂志，2015，50(12)：881-887.
     [7]孙冬华，何援利，张冬梅，等. 不同宫腔粘连评分标准对宫腔粘连疾病预后的预测作用分析[J]. 解放军医学杂志，2017，42(5)：439-444.
     [8]杜杉珊，赵宏利. 宫腔粘连中医研究进展[J]. 山西中医学院学报，2016，17(1)：69-71.
     [9]李丹，何嘉琳. 宫腔粘连中西医研究进展[J]. 浙江临床医学，2015，17(6)：1029-1031.
     [10]Healy MW， Schexnayder B， Connell MT， et al. Intrauterine adhesion prevention after hysteroscopy： a systematic review and meta-analysis[J]. Am J Obstet Gynecol，2016，215(3)：267-275.
     [11]周蕊敏. 稽留流产清宫术后宫腔粘连危险因素的病例对照研究[J]. 医药论坛杂志，2021，42(3)：45-47.
     [12]鲁静洁，朱慧，朱湘虹，等. 宫腔粘连分离术后复发为重度宫腔粘连的因素分析[J]. 实用妇产科杂志，2017，33(10)：751-754.
     [13]Wang C， Li X， Meng X， et al. Prevention of experimental postoperative peritoneal adhesions through the intraperitoneal administration of tanshinone IIA[J]. Planta Med，2014，80(12)：969-973.
     [14]Yao Q， Zheng YW， Lan QH， et al. Aloe/poloxamer hydrogel as an injectable beta-estradiol delivery scaffold with multi-therapeutic effects to promote endometrial regeneration for intrauterine adhesion treatment[J]. Eur J Pharm Sci，2020，148：105316.
     [15]Cao J， Liu D， Zhao S， et al. Estrogen attenuates TGF-beta1-induced EMT in intrauterine adhesion by activating Wnt/beta-catenin signaling pathway[J]. Braz J Med Biol Res，2020，53(8)：e9794.
     [16]罗小雨，彭菊兰，吴璇华. TGF-β和TIMP-1在宫腔粘连患者血清中的表达[J]. 宁夏医科大学学报，2013，35(10)：1143-1145.
     [17]Askari N， Ghazanfari T， Naghizadeh MM， et al. Evaluation of association between the serum levels of MMP-9 and MMP-9/TIMPs with soluble forms ofselectins and itching induced by sulfur mustard[J]. Iran J Pathol，2017，12(3)：257-264.
     [18]Kittiwattanokhun A， Samosorn S， Innajak S， et al. Inhibitory effects on chondrosarcoma cell metastasis by Senna alata extract[J]. Biomed Pharmacother，2021，137(11)：111337.
     [19]Li C， Wang W， Sun S， et al. Expression and potential role of MMP-9 in intrauterine adhesion[J]. Mediators Inflamm， 2021：6676510.
     [20]尚雪，孙广范，关燕鸣，等. 宫腔粘连分离术对宫腔粘连患者子宫内膜基质金属蛋白酶-9表达的影响[J]. 中国实用医药，2018，13(14)：83-84.
     [21]章晓乐，迟令侃，张琼，等. 宫腔粘连患者月经血中与ECM降解相关因子的表达及意义[J]. 生殖医学杂志，2019，28(5)：556-559.
     [22]Cabral-Pacheco GA， Garza-Veloz I， Castruita-De LRC， et al. The roles of matrix metalloproteinases andtheir inhibitors in human diseases[J]. Int J Mol Sci， 2020，21(24)：9739.
     [23]Ferretti G， Bacchetti T， Banach M， et al. Impact of statin therapy on plasma MMP-3， MMP-9， and TIMP-1 concentrations： asystematic review and Meta-analysis of randomized placebo-controlled trials[J]. Angiology， 2017， 68(10)：850-862.

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