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硫芥诱导的长期肺部并发症的血清基质金属蛋白酶及其组织抑制剂谱:伊朗萨达尔什特队列研究(SICS)。

Serum profiles of matrix metalloproteinases and their tissue inhibitors in long-term pulmonary complication induced by sulfur mustard: Sardasht-Iran Cohort Study (SICS).

机构信息

Pharmacology Toxicology Department, School of Pharmacy, Shahid Behashti University of Medical Sciences, Tehran, Islamic Republic of Iran; Pharmacology Toxicology Department, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Islamic Republic of Iran.

出版信息

Int Immunopharmacol. 2013 Nov;17(3):964-7. doi: 10.1016/j.intimp.2012.12.025. Epub 2013 Jan 29.

Abstract

Sulfur mustard (SM) is a cytotoxic chemical agent which can cause severe irritation and irreversible damages to body tissues. The effect of SM gas on respiratory tract is one of the main causes of short and long term disabling complications. Matrix metalloproteinases (MMPs) have a critical role in controlling extra cellular matrix remodeling and inflammatory responses in lung tissue and are involved in many various chronic pulmonary diseases. The aim of the present study was to evaluate the possible role of MMPs and their endogenous inhibitors in SM induced lung symptoms in exposed subjects 20 years after exposure. Serum level of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 was measured by ELISA and compared between groups of exposed without any symptoms (control group) and with mild or moderate-severe lung complications. MMP-2 and MMP-9 activity was assayed by gelatin zymography method. There was a significant association between serum level of MMP-1 and severity of lung complications in SM exposed groups. MMP-2 activity was decreased in exposed groups with mild lung complications. TIMPs level was not different in exposed and normal groups. We concluded that increased serum levels of MMP-1 and decreased MMP-2 activity may have roles in pathogenesis and persistence of lung complications in SM exposed victims.

摘要

芥子气(SM)是一种细胞毒性化学战剂,可对人体组织造成严重刺激和不可逆转的损伤。SM 气体对呼吸道的影响是导致短期和长期致残并发症的主要原因之一。基质金属蛋白酶(MMPs)在控制肺组织细胞外基质重塑和炎症反应方面起着关键作用,并且与许多慢性肺部疾病有关。本研究旨在评估 MMPs 及其内源性抑制剂在 SM 暴露 20 年后暴露人群肺部症状中的可能作用。通过 ELISA 法测定 MMP-1、MMP-2、MMP-8、MMP-9、TIMP-1、TIMP-2、TIMP-3 和 TIMP-4 的血清水平,并比较无任何症状(对照组)和有轻度或中度-重度肺部并发症的暴露组之间的差异。通过明胶酶谱法测定 MMP-2 和 MMP-9 的活性。在 SM 暴露组中,MMP-1 血清水平与肺部并发症的严重程度之间存在显著相关性。MMP-2 活性在有轻度肺部并发症的暴露组中降低。暴露组和正常组的 TIMP 水平无差异。我们得出结论,MMP-1 血清水平升高和 MMP-2 活性降低可能在 SM 暴露受害者肺部并发症的发病机制和持续存在中起作用。

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