[1]吴 慧a,韩文龙b,柏 蕾,等.胎膜早破产妇血清SFRP5，TIMP-1 和HMGB1 水平与并发组织学绒毛膜羊膜炎的相关性研究[J].现代检验医学杂志,2022,37(05):112-117+158.[doi:10.3969/j.issn.1671-7414.2022.05.022]
　WU Huia,HAN Wen-longb,BO Lei,et al.Correlation of Serum SFRP5, TIMP-1 and HMGB1 Levels with Histological Chorioamnitis in Pregnant Women with Premature Rupture of Membranes[J].Journal of Modern Laboratory Medicine,2022,37(05):112-117+158.[doi:10.3969/j.issn.1671-7414.2022.05.022]
点击复制

胎膜早破产妇血清SFRP5，TIMP-1 和HMGB1 水平与并发组织学绒毛膜羊膜炎的相关性研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年05期
页码:
112-117+158
栏目:
论著
出版日期:
2022-09-15

文章信息/Info

Title:
Correlation of Serum SFRP5, TIMP-1 and HMGB1 Levels with Histological Chorioamnitis in Pregnant Women with Premature Rupture of Membranes
文章编号:
1671-7414（2022）05-112-07
作者:
吴 慧1a; 韩文龙1b; 柏 蕾2; 孙红丽1a
1. 河北生殖妇产医院a. 产科；b. 医学检验科, 石家庄 050090；2. 济宁医学院附属医院妇产科, 山东济宁 272001
Author(s):
WU Hui1a ; HAN Wen-long1b;  BO Lei2;  SUN Hong-li1a
1a.Department of Obstetrics；1b.Department of Medical Laboratory, Hebei Maternity Hospital,Shijiazhuang 050090, China；2.Department of Obstetrics and Gynecology, Affiliated Hospital of Jining Medical College,Shandong Jining 272001,China
关键词:
胎膜早破; 分泌型卷曲相关蛋白5; 基质金属蛋白酶组织抑制剂 1; 高迁移率族蛋白B1; 组织学绒毛膜羊膜炎
分类号:
R714.433；R446.11
DOI:
10.3969/j.issn.1671-7414.2022.05.022
文献标志码:
A
摘要:
目的　探讨胎膜早破（premature rupture of membranes，PROM）产妇血清分泌型卷曲相关蛋白5（secretedfrizzled-related protein-5，SFRP5）、基质金属蛋白酶组织抑制剂 1（tissue inhibitor of metalloproteinase 1，TIMP- 1）和高迁移率族蛋白B1（high mobility group protein B1，HMGB1）水平与组织学绒毛膜羊膜炎（histologic chorioamnionitis，HCA）的关系。方法　选择2019 年6 月～ 2021 年8 月河北生殖妇产医院产科收治的72 例足月PROM 并发HCA 产妇（HCA 组），120 例足月PROM 未发生HCA 产妇（非HCA 组）和51 例足月妊娠未发生PROM 产妇（对照组）。检测血清SFRP5，TIMP-1 和HMGB1 水平，分析其与PROM 产妇发生HCA 的关系。绘制受试者工作特征（ROC）曲线，分析SFRP5，TIMP-1 和HMGB1 诊断PROM 产妇发生HCA 的价值。结果　HCA 组血清SFRP5（7.53±1.42 mg/L）和TIMP-1（102.35±16.67 ng/ml ）水平低于非HCA 组（10.23±2.11 mg/L，185.23±29.42 ng/ml）和对照组（15.23±3.06mg/L，242.13±32.65 ng/ml），差异均有统计学意义（F =187.726, 423.352，均P ＜ 0.05）；血清HMGB1 水平（10.25±3.26ng/ml）高于非HCA 组（6.02±1.41 ng/ml）和对照组（3.06±0.81 ng/ml），差异有统计学意义（F=191.968，P ＜ 0.05）。多因素Logistic 回归分析示PROM 破膜时间≥ 48h[OR=2.208，95 ％ CI=1.466 ～ 3.326）]， 阴道检查次数≥ 3 次[OR=1.540，95％ CI=1.206 ～ 1.968）]，SFRP5 ＜ 7.53mg/L[OR=1.657，95％ CI=1.220 ～ 2.250）]，TIMP-1 ＜ 102.35ng/ml[OR=1.826，95 ％ CI=1.275 ～ 2.613）] 和HMGB1 ≥ 10.25ng/ml[OR=1.809，95 ％ CI=1.237 ～ 2.647] 是PROM 产妇发生HCA 的危险因素（均P ＜ 0.05）。SFRP5，TIMP-1 和HMGB1 诊断足月PROM 产妇发生HCA 的曲线下面积分别为0.707，0.731 和0.747，联合诊断曲线下面积为0.933，高于单独指标（Z=5.822，5.611，5.274，均P=0.000）。结论　PROM 产妇血清SFRP5 和TIMP-1 水平降低，HMGB1 水平升高，且与HCA 发病密切相关。SFRP5，TIMP-1 和HMGB1 可作为HCA 诊断的生物标志物。
Abstract:
Objective　To investigate the relationship between serum secreted frizzled-related protein-5 (SFRP5), tissue inhibitor of metalloproteinase 1 (TIMP-1), high mobility group protein B1 (HMGB1) and histologic chorioamnionitis (HCA) in pregnant women with premature rupture of membranes (PROM).Methods　From June 2019 to August 2021, 72 cases of full-term PROM with HCA (HCA group), 120 cases of full-term PROM without HCA (non-HCA group) and 51 cases of full-term pregnancy without PROM (control group) from Hebei Maternity Hospital were selected.Serum level of SFRP5, TIMP-1 and HMGB1 were detected to analyze the relationship between SFRP5, TIMP-1 and HMGB1 and HCA in PROM parturient women.Receiver operating characteristic curve (ROC) was drawn to analyze the value of SFRP5, TIMP-1 and HMGB1 in diagnosing HCA in PROM parturient. Results　The levels of serum SFRP5 （7.53±1.42 mg/L）and TIMP-1（102.35±16.67 ng/ml）in HCA group were lower than those in non-HCA group（10.23±2.11 mg/L，185.23±29.42 ng/ml）and control group（15.23±3.06mg/L，242.13±32.65 ng/ml）, the differences were statistically significant （F =187.726, 423.352，all P ＜ 0.05）, and the levels of serum HMGB1 （10.25±3.26 ng/ml）were higher than those in non-HCA group （6.02±1.41 ng/ml）and control group （3.06±0.81 ng/ml），the difference was statistically significant（F=191.968，P ＜ 0.05）.Multivariate Logistic regression analysis showed that PROM rupture time ≥ 48h [OR=2.208，95%CI=1.466 ～ 3.326）], vaginal examination times ≥ 3[OR=1.540，95%CI=1.206 ～ 1.968）], SFRP5 ＜ 7.53mg/L[OR=1.657，95%CI=1.220 ～ 2.250）]，TIMP-1 ＜ 102.35ng/ ml[OR=1.826，95%CI=1.275 ～ 2.613）] and HMGB1 ≥ 10.25ng/ml[OR=1.809，95%CI=1.237 ～ 2.647] were risk factors for HCA in PROM parturient women（ all P＜0.05）.The area under the curve of SFRP5, TIMP-1 and HMGB1 were 0.707, 0.731 and 0.747, respectively, and the area under the curve of SFRP5, TIMP-1 and HMGB1 were 0.933, higher than the single index (Z=5.822, 5.611 and 5.274, all P ＜ 0.05). Conclusion　The serum levels of SFRP5 and TIMP-1 in PROM maternal decreased, while the serum level of HMGB1 increased, which were closely related to the pathogenesis of HCA. SFRP5, TIMP-1 and HMGB1 can be used as biomarkers for the diagnosis of HCA.

参考文献/References:

[1] ASSEFA N E, BERHE H, GIRMA F, et al. Risk factors of premature rupture of membranes in public hospitals at Mekele city, Tigray, a case control study[J]. BMC Pregnancy and Childbirth, 2018, 18(1): 386.
[2] ROUZAIRE M, CORVAISIER M, ROUMEAU V, et al.Predictors of short latency period exceeding 48 h after preterm premature rupture of membranes[J]. Journal of Clinical Medicine, 2021, 10(1): 150.
[3] BALCIUNIENE G, GULBINIENE V, DUMALAKIENE I, et al. Prognostic markers for chorioamnionitis:IL-6, TNF-α, and MMP-8 in vaginally obtained amniotic fluid[J]. Journal of Clinical Medicine, 2021, 10(5):1136.
[4] SUN Minghui, WANG Weijun, MIN Lingtian, et al.Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway[J].Journal of Orthopaedic Surgery and Research, 2021,16(1): 129.
[5] LITWINIUK M, RADOWICKA M, KREJNER A, et al.The MMP-9/TIMP-1 imbalance and the reduced level of TGF-β in the cervical area of amniotic membrane is a possible risk factor of PROM and premature labor - proof-of-concept study[J]. Ginekologia Polska, 2017,88(7): 379-384.
[6] YAN Huan, ZHU Linlin, ZHANG Zhan, et al. HMGB1-RAGE signaling pathway in pPROM[J]. Taiwanese Journal of Obstetrics & Gynecology, 2018, 57(2): 211-216.
[7] 中华医学会妇产科学分会产科学组.胎膜早破的诊断与处理指南(2015)[J]. 中华围产医学杂志, 2015,18(3):161-167.
Obstetrics Subgroup , Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Guidelines for diagnosis and management of premature rupture of membranes (2015) [J]. Chinese Journal of Perinatal Medicine,2015,18(3):161-167.
[8] 郭莉, 刘芳, 陈蔚瑜, 等. 胎盘组织学绒毛膜羊膜炎与相关临床症状和检验指标的关系[J]. 广东医学,2016, 37(z1):80-82.
GUO Li, LIU Fang, CHEN Weiyu, et al.Placental histology chorioamnitis in relation to associated clinical symptoms and test indicators[J]. Guangdong Medical Journal, 2016,37(z1)：80-82.
[9] BIERSTONE D, WAGENAAR N, GANO D L,et al. Association of histologic chorioamnionitis with perinatal brain injury and early childhood neurodevelopmental outcomes among preterm neonates[J]. JAMA Pediatrics, 2018, 172(6): 534-541.
[10] MA Yan, XU Yun, JIANG Lijuan, et al. Application of a prediction model based on the laboratory index score in prelabor rupture of membranes with histologic chorioamnionitis during late pregnancy[J]. Medical Science Monitor, 2020, 26: e924756.
[11] LIU Lingbin, CHEN Xiaodong, ZHOU Xiangyu, et al.The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus[J]. Bioscience Reports, 2018,38(4): BSR20180011.
[12] DU Yu, ZHAO Yingxin, ZHU Yong, et al. High serum secreted Frizzled-Related protein 5 levels associates with early improvement of cardiac function following ST-Segment elevation myocardial infarction treated by primary percutaneous coronary intervention[J]. Journal of Atherosclerosis and Thrombosis, 2019, 26(10): 868-878.
[13] SCHULZ J, KNAPPE C, GRAETZ C, et al. Secreted frizzled-related protein 5 serum levels in human periodontitis-A nested case-control study[J]. Journal of Clinical Periodontology, 2019, 46(5): 522-528.
[14] PENG Chuan, XIAO Xiaoqiu, KANG Bing, et al.Serum secreted frizzled-related protein 5 levels differentially decrease in patients with hepatitis B virus-associated chronic infection and hepatocellular carcinoma[J]. Oncology Letters, 2014, 8(3): 1340-1344.
[15] PRATS-PUIG A, SORIANO-RODR?GUEZ P,CARRERAS-BADOSA G, et al. Balanced duo of antiinflammatory SFRP5 and proinflammatory WNT5A in children[J]. Pediatric Research, 2014, 75(6): 793-797.
[16] 郭琦, 李巧云, 童嘉宁. 胎膜中 MMP -9, TIMP -1,TIMP -2, TGF -β1 表达与胎膜早破的关系[J]. 广东医学, 2014, 35(8):1197-1199, 1200.
GUO Qi, LI Qiaoyun, TONG Jianing. Relationship between expression of MMP-9,TIMP-1,TIMP-2,TGF-β1 and premature rupture of membranes[J].Guangdong Medical Journal, 2014,35(8):1197-1199,1200.
[17] VINCENT Z L, MITCHELL M D, PONNAMPALAM A P. Regulation of TIMP-1 in human placenta and fetal membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine[J]. Reproductive Biology and Endocrinology : RB&E, 2015, 13: 136.
[18] FUKUNAGA S, ICHIYAMA T, MAEBA S, et al.MMP-9 and TIMP-1 in the cord blood of premature infants developing BPD[J]. Pediatric Pulmonology,2009, 44(3): 267-272.
[19] A ?LAMAZIAN ? K, BOLOTSKIKH M V,KOSTIUCHEK I N, et al. Morphological features of placenta and expression of collagen-6, MMP-1 and TIMP-1 in placental membranes of women with premature rupture of membranes[J]. Arkhiv Patologii,2012, 74(1): 42-45.
[20] 刘莉, 张军. 急性脑梗死患者血清hs-CRP,TNF-α和TIMP-1 水平检测在疾病预后评估中的应用价值[J]. 现代检验医学杂志, 2018, 33(5):87-90, 94.
LIU Li, ZHANG Jun. Value of serum hs-CRP,TNF-α and TIMP-1 levels in prognostic evaluation of patients with acute cerebral infarction [J]. Journal of Modern Laboratory Medicine, 2018, 33(5):87-90,94.
[21] BAUMBUSCH M, BUHIMSCHI C S, OLIVER E A,et al. High mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intraamniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes[J].Cytokine, 2016, 81: 82-87.
[22] QIU Xiaoyuan, SUN Lu, HAN Xueling, et al. Alarmin high mobility group box-1 in maternal serum as a potential biomarker of chorioamnionitis-associated preterm birth[J]. Gynecological Endocrinology, 2017,33(2): 128-131.

相似文献/References:

[1]张 赟,李 娅,郭旭昌,等.胎膜早破孕妇生殖道感染病原菌的分布及耐药性分析[J].现代检验医学杂志,2015,30(03):98.[doi:10.3969/j.issn.1671-7414.2015.03.028]
　ZHANG Yun,LI Ya,GUO Xu-chang,et al.Distribution and Drug Resistance of Genital Tract Pathogenic Bacteria in Pregnant Women with Premature Rupture of Membrane[J].Journal of Modern Laboratory Medicine,2015,30(05):98.[doi:10.3969/j.issn.1671-7414.2015.03.028]
[2]李小侠a,解 娟a,詹 颉a,等.围产期胎膜早破与生殖道病原菌感染的分析[J].现代检验医学杂志,2016,31(04):90.[doi:10.3969/j.issn.16717-414.2016.04.024]
　LI Xiao-xiaa,XIE Juana,ZHAN Jiea,et al.Analysis of Perinatal Premature Rupture of Membranes and Reproductive Tract Pathogen Infection[J].Journal of Modern Laboratory Medicine,2016,31(05):90.[doi:10.3969/j.issn.16717-414.2016.04.024]
[3]王　麟,陈惠新,李小燕.慢性心力衰竭患者血清TRPC1,sFRP5和NT-proBNP水平与心功能及疾病严重程度的临床研究[J].现代检验医学杂志,2021,36(06):6.[doi:10.3969/j.issn.1671-7414.2021.06.002]
　WANG Lin,CHEN Hui-xin,LI Xiao-yan.Study on the Relationship between Serum TRPC1, sFRP5 and NT-proBNP Levels and Cardiac Function and Disease Severity in Predicting with Chronic Heart Failure[J].Journal of Modern Laboratory Medicine,2021,36(05):6.[doi:10.3969/j.issn.1671-7414.2021.06.002]
[4]杨 柳,付 欣,张小飞.胎膜早破孕妇生殖道无乳链球菌血清型分型和耐药基因分析[J].现代检验医学杂志,2023,38(03):123.[doi:10.3969/j.issn.1671-7414.2023.03.022]
　YANG Liu,FU Xin,ZHANG Xiao-fei.Serotyping and Resistance Gene Analysis of Reproductive Streptococcus Agalactiae in Women with Premature Rupture of Membranes[J].Journal of Modern Laboratory Medicine,2023,38(05):123.[doi:10.3969/j.issn.1671-7414.2023.03.022]
[5]裔 静,康苧心,卢海波,等.慢性鼻窦炎患者血清和鼻腔分泌物中分泌型卷曲相关蛋白5 的表达水平及临床价值研究[J].现代检验医学杂志,2023,38(06):103.[doi:10.3969/j.issn.1671-7414.2023.06.019]
　YI Jing,KANG Ningxin,LU Haibo,et al.Study on the Expression Level and Clinical Value of Secretory Frizzledrelated Protein 5 in Serum and Nasal Secretions in Patients with Chronic Rhinosinusitis[J].Journal of Modern Laboratory Medicine,2023,38(05):103.[doi:10.3969/j.issn.1671-7414.2023.06.019]
[6]吴迎爽a,薛向东a,杜志辉a,等.特发性矮小症患儿血清Vaspin和SFRP5水平表达及其诊断价值研究[J].现代检验医学杂志,2024,39(01):95.[doi:10.3969/j.issn.1671-7414.2024.01.017]
　WU Yingshuanga,XUE Xiangdonga,DU Zhihuia,et al.Expression of Serum Vaspin and SFRP5 in Children with Idiopathic Nanosomia and Their Diagnostic Value[J].Journal of Modern Laboratory Medicine,2024,39(05):95.[doi:10.3969/j.issn.1671-7414.2024.01.017]

备注/Memo

备注/Memo:
基金项目：河北省医学科学研究课题（20191408），资助单位：河北省卫生健康委员会。
作者简介：吴慧（1981-），女，本科，副主任医师，研究方向：早产专病，E-mail：b5u89rch12@21cn.com。
更新日期/Last Update: 2022-09-15