Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia
Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia
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DOI：
10.1097/01.ccm.0000127778.16609.ec
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发表时间：
2004-06-01
影响因子：
8.8
通讯作者：
Schulz, R
中科院分区：
文献类型：
--
作者：
Lalu, MM;Csont, T;Schulz, R
目的：研究内毒素血症期间心肌和血浆基质金属蛋白酶（MMP）活性是否改变。设计：前瞻性随机动物研究。设置：大学研究实验室。受试者：雄性Sprague-Dawley大鼠，250-300 g。干预。给大鼠施用细菌脂多糖（LPS）或溶媒（无热原水）。在注射后0.5、1、3、6、12和24小时处死给予LPS的动物组。在6小时时处死媒介物注射的动物。处死前记录血压。心脏和血浆样品进行了分析，明胶酶谱和immunoblot. Measures和主要结果：血压显着降低，在3-24小时后LPS注射，然而，明显的症状内毒素血症和降低血压是最显着的6-12小时后LPS。对照组大鼠的心脏样品显示MMP-2活性，但没有MMP-9活性。当内毒素血症的明显症状在6-12小时达到峰值时，MMP-2活性显著降低。血浆MMP-2活性在注射LPS后3-12小时显著降低。这种活性的丧失与MMP-2蛋白的丧失有关。与此相反，血浆MMP-9活性迅速升高后LPS注射，峰值之间的1和12小时。结论：内毒素血症可引起心肌和血浆MMP活性的快速变化。循环MMP-9活性的增加可能有助于内毒素血症性心血管功能障碍。
Objective: To investigate whether myocardial and plasma matrix metalloproteinase (MMP) activities are altered during endotoxemia.Design: Prospective randomized, animal study.Setting: University research laboratory.Subjects: Male Sprague-Dawley rats, 250-300 g.Interventions. Rats were administered either bacterial lipopolysaccharide (LPS) or vehicle (pyrogen-free water). Groups of LPS-administered animals were killed at 0.5, 1, 3, 6, 12, and 24 hrs postinjection. Vehicle injected animals were killed at 6 hrs. Blood pressure was recorded before kill. Heart and plasma samples were analyzed by gelatin zymography and immunoblot.Measurements and Main Results: Blood pressure was significantly depressed at 3-24 hrs post-LPS injection; however, overt symptoms of endotoxemia and reduction in blood pressure were most significant 6-12 hrs post-LPS. Heart samples from control rats revealed MMP-2 activity but no MMP-9 activity. MMP-2 activity was significantly depressed when overt symptoms of endotoxemia peaked at 6-12 hrs. Plasma MMP-2 activity significantly decreased 3-12 hrs after LPS injection. This loss of activity was associated with a loss of MMP-2 protein. In contrast, plasma MMP-9 activities were rapidly elevated following LPS injection, peaking between 1 and 12 hrs. MMP-9 activity correlated inversely with blood pressure.Conclusions: Endotoxemia induced rapid changes in MMP activity in both the myocardium and plasma. An increase in circulating MMP-9 activity may contribute to endotoxemic cardiovascular dysfunction.