Differential release of matrix metalloproteinase-9 and nitric oxide following infusion of endotoxin to human volunteers
Differential release of matrix metalloproteinase-9 and nitric oxide following infusion of endotoxin to human volunteers
复制标题
DOI：
10.1034/j.1399-6576.2003.00059.x
复制
发表时间：
2003-04-01
影响因子：
2.1
通讯作者：
Radomski, MW
中科院分区：
文献类型：
--
作者：
Albert, J;Radomski, A;Radomski, MW
背景：仅在美国每年就有大约40万例脓毒症发生，这与很高的死亡率有关。细菌脂多糖(LPS)在脓毒症中触发全身炎症反应。然而，内毒素启动的下游细胞级联仍在阐明中。一氧化氮(NO)和基质金属蛋白酶-2和-9(MMP2和MMP9)被认为是由内毒素诱导的。方法：10名健康志愿者静脉滴注iPS(2 ng kg(-1))，观察注射后NO、MMP2和MMP9的释放。在实验开始之前，受试者被放置了静脉导管。同时放置并持续监测心电图机。用耳温计测量体温，每隔10min采集静脉血，用酶谱法检测血浆中基质金属蛋白酶-2和基质金属蛋白酶-9的含量，用高效液相色谱法测定一氧化氮代谢产物亚硝酸盐和硝酸盐的含量。结果：注射脂多糖可引起体温升高和心动过速。在注射内毒素后2 h，MMP9的释放呈时间依赖性，较基线增加30倍，达到高峰。脂多糖对基质金属蛋白酶-2活性无明显影响(P>；0.05)。输注内毒素对亚硝酸盐和硝酸盐水平无明显影响(从60+/-11到67+/-10微米，P>；0.05)。结论：内毒素血症的敏感指标是释放基质金属蛋白酶-9，而不是基质金属蛋白酶-2或一氧化氮。基质金属蛋白酶-9的释放可能通过对血管系统的促炎作用而参与脓毒症的发病。
Background: Roughly 400 000 cases of sepsis occur every year in the United States only and this is associated with a very high mortality. Bacterial lipopolysaccharide (LPS) triggers systemic inflammatory reactions in sepsis. However, down-stream cellular cascade initiated by LPS is still being elucidated. Nitric oxide (NO) and matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are known to be induced by LPS. We have investigated the release of NO, MMP-2 and MMP-9 following infusion of LPS to volunteers.Methods: IPS (2 ng kg(-1) ) was infused to 10 healthy volunteers. Before the experiments were started the subjects had an intravenous catheters placed. An electrocardiogram was also placed and monitored constantly. Body temperature was measured by ear thermometer every 10 min Venous blood was collected and cell-free plasma assayed for the presence of MMP-2 and MMP-9 using zymography and NO using HPLC assay for NO metabolites, nitrite and nitrate.Results: The administration of LPS resulted in increased body temperature and tachycardia. Time-dependent release of MMP-9(30 fold increase from the baseline) peaking at 2 h following infusion of LPS was observed. LPS did not significantly modify the activity of MMP-2 (P>0.05). Infusion of LPS did not significantly change the levels of nitrite and nitrate (from 60+/-11 to 67+/-10 mum, P>0.05).Conclusion: The release of MMP-9, but not MMP-2 or NO, is a sensitive index of endotoxaemia in humans. MMP-9 release may contribute to the pathogenesis of sepsis via its pro-inflammatory effects on the vasculature.