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基质金属蛋白酶及其抑制剂在沙眼衣原体感染的复发性自然流产患者子宫内膜细胞外基质周转中的作用。

Involvement of matrix metalloproteinases and their inhibitors in endometrial extracellular matrix turnover in Chlamydia trachomatis-infected recurrent spontaneous aborters.

作者信息

Singh Namita, Prasad Priya, Das Banashree, Rastogi Sangita

机构信息

Microbiology laboratory, National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi-110 029, India.

Department of Obstetrics and Gynaecology, Vardhaman Mahavir Medical College and Safdarjung Hospital, Ring Road, New Delhi-110 029, India.

出版信息

Pathog Dis. 2017 Jan 1;75(1). doi: 10.1093/femspd/ftx007.

DOI:10.1093/femspd/ftx007
PMID:28115359
Abstract

Mechanism underlying Chlamydia trachomatis disease pathology is not completely understood. It was hypothesised that dysregulation of extracellular matrix by matrix metalloproteinases (MMPs) might be involved in sequelae of events leading to abortion in C. trachomatis-infected women. Hence, this study was undertaken to elucidate the expression of MMP-2/MMP-9/TIMP-1/TIMP-3 in infected recurrent spontaneous aborters (RSA) and simultaneously ascertain effect of few cytokines (TNF-α, TGF-β1, TGF-β2)/cyclooxygenase-2 (Cox-2) on MMPs. Endometrial curettage tissue was collected from 135 RSA (group I) and 120 age-matched controls (group II) at Department of Obstetrics and Gynecology, SJH, New Delhi (India). PCR was performed for diagnosis of C. trachomatis MOMP/plasmid gene. Expression of MMP-2/MMP-9/TIMP-1/TIMP-3 mRNA was assessed by quantitative real-time PCR. Data were statistically evaluated. 15.6% (n = 21) RSA (Group-I) were diagnosed as C. trachomatis positive. Significant upregulation of MMP-2/MMP-9 and decreased TIMP-1/TIMP-3 were found in C. trachomatis-positive RSA (group I) versus control women (group II). MMP-2 was found positively correlated with cytokines/Cox-2. Significant positive correlation was observed between MMP-2/MMP-9 and C. trachomatis copy load. Overall data suggested that dysregulated MMPs/TIMPs promoted excessive endometrial matrix degradation which, in turn, affected pregnancy leading to spontaneous abortion in infected women.

摘要

沙眼衣原体疾病病理的潜在机制尚未完全明确。有假说认为,基质金属蛋白酶(MMPs)对细胞外基质的失调可能参与了导致沙眼衣原体感染女性流产的一系列后续事件。因此,本研究旨在阐明MMP - 2/MMP - 9/TIMP - 1/TIMP - 3在反复自然流产感染患者(RSA)中的表达情况,并同时确定几种细胞因子(TNF-α、TGF-β1、TGF-β2)/环氧化酶-2(Cox-2)对MMPs的影响。在印度新德里SJH妇产科,从135例反复自然流产患者(I组)和120例年龄匹配的对照者(II组)收集了子宫内膜刮除组织。进行PCR以诊断沙眼衣原体主要外膜蛋白/质粒基因。通过定量实时PCR评估MMP - 2/MMP - 9/TIMP - 1/TIMP - 3 mRNA的表达。对数据进行统计学评估。15.6%(n = 21)的反复自然流产患者(I组)被诊断为沙眼衣原体阳性。与对照女性(II组)相比,沙眼衣原体阳性的反复自然流产患者(I组)中MMP - 2/MMP - 9显著上调,TIMP - 1/TIMP - 3降低。发现MMP - 2与细胞因子/Cox-2呈正相关。MMP - 2/MMP - 9与沙眼衣原体拷贝数负荷之间存在显著正相关。总体数据表明,MMPs/TIMPs失调促进了子宫内膜基质的过度降解,进而影响妊娠,导致感染女性自然流产。

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