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基质金属蛋白酶-9 作为创伤和感染引起的多器官功能障碍综合征严重程度的新生物标志物。

Matrix metalloproteinase-9 as new biomarkers of severity in multiple organ dysfunction syndrome caused by trauma and infection.

机构信息

Department of Cardiology, The First People's Hospital of Yichang/The People's Hospital of Three Gorges University, Yichang, Hubei Province, People's Republic of China.

出版信息

Mol Cell Biochem. 2012 Jan;360(1-2):271-7. doi: 10.1007/s11010-011-1066-0. Epub 2011 Oct 1.

Abstract

Multiple organ dysfunction syndrome (MODS) is an important cause of morbidity and mortality in intensive care unit. A severe insult in the form of infection or trauma primes the host immune system so that a subsequent, relatively trivial insult produces systemic inflammation response syndrome, which can lead to MODS and death. Matrix metalloproteinase-9 (MMP-9) is stored in the tertiary granules of polymorphonuclear leukocytes. These cells are key effectors in acute inflammatory diseases, such as sepsis and MODS. Endotoxin leads to rapid release of MMP-9 from these granules in vitro and in vivo. However, the role of this enzyme in MODS, and whether it is associated with organ injury at the early stage of MODS remains unclear. This present work may study role of MMP-9 with the MODS rats that caused by trauma and infection and investigate the mechanism of organ injury at the early stage of MODS. Here, we developed a rat model for MODS caused by trauma and infection and analyzed the dynamic level of MMP-9 and determined the relationship between MMP-9 level and early phase of organ injury in MODS rat. The histological changes in pulmonary, renal, and hepatic tissue were observed by light microscope. The expressions of plasma MMP-9 proteins were detected by an enzyme linked immunosorbent assay and its levels in the pulmonary, renal, and hepatic tissue were detected by using immunohistochemistry, respectively. The results indicated that there were no significant improvements in histopathology of rats in control group. However, the pulmonary, renal, and hepatic damage were serious in MODS groups. The concentration of MMP-9 in plasma and tissues of MODS rats increased markedly at the early stage and were higher than that of the control group. Moreover, the MMP-9 level in plasma positively correlated with the levels of pulmonary, renal, and hepatic tissue. This study clearly shows that MMP-9 is good biomarker to predict the severity of injury organ at the early phase of MODS.

摘要

多器官功能障碍综合征(MODS)是重症监护病房发病率和死亡率的重要原因。感染或创伤等严重损伤使宿主免疫系统处于预备状态,随后相对轻微的损伤会引发全身炎症反应综合征,从而导致 MODS 和死亡。基质金属蛋白酶-9(MMP-9)储存在多形核白细胞的三级颗粒中。这些细胞是急性炎症性疾病(如败血症和 MODS)的关键效应物。内毒素在体外和体内导致这些颗粒中 MMP-9 的快速释放。然而,这种酶在 MODS 中的作用,以及它是否与 MODS 早期的器官损伤有关尚不清楚。本研究可能会研究创伤和感染引起的 MODS 大鼠中 MMP-9 的作用,并探讨 MODS 早期器官损伤的机制。在这里,我们建立了创伤和感染引起的 MODS 大鼠模型,并分析了 MMP-9 的动态水平,确定了 MMP-9 水平与 MODS 大鼠早期器官损伤的关系。通过光镜观察肺、肾和肝组织的组织学变化。通过酶联免疫吸附试验检测血浆 MMP-9 蛋白的表达,并分别通过免疫组织化学法检测肺、肾和肝组织中 MMP-9 的水平。结果表明,对照组大鼠的组织病理学无明显改善。然而,MODS 组的肺、肾和肝损伤严重。MODS 大鼠血浆和组织中 MMP-9 浓度在早期明显增加,且高于对照组。此外,血浆中 MMP-9 水平与肺、肾和肝组织水平呈正相关。本研究清楚地表明,MMP-9 是预测 MODS 早期损伤器官严重程度的良好生物标志物。

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