Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

IntroductionMatrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients.MethodsIn this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied.ResultsPlasma MMP-8 and -9 were higher in patients than in healthy controls (PP = 0.016), but only MMP-8 differed between the TBSA20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P20% groups (P引言 基质金属蛋白酶（Matrix metalloproteinases, MMPs）-8与-9由中性粒细胞在急性炎症过程中释放，可能参与烧伤后的通透性改变。既往针对脓毒症的回顾性研究显示，MMP-8、MMP-9及金属蛋白酶组织抑制剂-1（tissue inhibitor of metalloproteinase-1, TIMP-1）的水平与健康对照存在差异，且TIMP-1与患者预后具有相关性。本研究旨在探讨上述蛋白与烧伤患者病情严重程度及预后的关系。 方法 本研究为一项前瞻性、观察性双中心研究，采集烧伤患者入院至伤后21天的血浆样本，以及入院时的烧伤水疱液样本。分别对比总体体表总面积（Total Body Surface Area, TBSA）≥20%的烧伤患者（N=30）与健康对照者，以及伤后90天存活者与非存活者之间的MMP-8、MMP-9及TIMP-1水平。同时对比两组患者伤后24~48小时的MMP-8、-9及TIMP-1水平、峰值水平及时间校正均值。分析上述蛋白水平与临床参数及烧伤面积的相关性，并对烧伤水疱液中的MMP-8、-9及TIMP-1水平进行研究。 结果 患者血浆中的MMP-8与MMP-9水平高于健康对照（P=0.016），但仅MMP-8在TBSA≥20%组间存在差异。MMP-8与MMP-9均与临床严重程度或预后指标无相关性。TIMP-1在患者与健康对照间差异显著，且在TBSA≥20%组间亦存在差异。