1)Immunoregulation Research Center, Shahed University, Tehran, I.R. Iran.2)Department of Immunology, Shahed University, Tehran, I.R. Iran.
Department of Immunology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, I.R. Iran.
Arch Iran Med. 2017 Feb;20(2):74-82.
Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure.
Totally, 372 male volunteers with a history of SM- exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique.
Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ± 2.836 vs. 1.546 ± 2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P = 0.013 respectively).
High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM-exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors.
基质金属蛋白酶（MMPs）是一类蛋白水解酶，具有强烈的降解细胞外基质各部分的能力。MMP 酶强烈参与正常组织重塑和伤口愈合等生理过程，以及肺部疾病的病理学。它们是对毒素等环境刺激物的反应而释放的，并受到内源性金属蛋白酶组织抑制剂（TIMPs）的调节。芥子气（SM）是一种化学毒素，可对肺部组织造成严重的永久性损伤。本研究旨在评估 MMP-9 和 TIMPs 在暴露于 SM 的患者暴露 20 年后 SM 引起的肺部症状和体征中的可能作用。
共有 372 名有 SM 暴露史的男性志愿者和 128 名年龄和性别匹配的未暴露对照者参与了研究，并分为三组：正常、轻度和中重度。所有参与者均进行临床评估和肺功能检查，并使用 ELISA 技术测量 MMP-9 及其抑制剂的血清浓度。
与 SM 暴露后肺部正常的个体相比，中重度肺部并发症的 SM 暴露组的 MMP-9 血清水平升高（2.321 ± 2.836 比 1.546 ± 2.176，P = 0.001），而只有 SM 暴露后肺部正常的个体中 MMP-9/TIMP-4 复合物升高（85 ± 265 比 82 ± 222，P = 0.025）。尽管 MMP-9 和其抑制剂与肺活量测定结果均无相关性，但在 SM 暴露患者慢性咳嗽和咯血中检测到循环 MMP-9 升高（分别为 P = 0.013 和 P = 0.013）。
高水平的组织破坏和重塑介质可能会影响 SM 暴露后的长期肺部结构。将临床评估与这些因素相关联可以有效地帮助我们识别重要的效应物。
