Pancreatic trypsin increases matrix metalloproteinase-9 accumulation and activation during acute intestinal ischemia-reperfusion in the rat
Pancreatic trypsin increases matrix metalloproteinase-9 accumulation and activation during acute intestinal ischemia-reperfusion in the rat
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DOI：
10.1016/s0002-9440(10)63729-7
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发表时间：
2004-05-01
影响因子：
6
通讯作者：
Schmid-Schönbein, GW
中科院分区：
文献类型：
--
作者：
Rosário, HS;Waldo, SW;Schmid-Schönbein, GW
肠道缺血再灌注会产生一系列炎症介质，最近已证明其起源与胰腺消化酶有关。基质金属蛋白酶-9 (MMP-9) 参与多种炎症过程，包括心肌、肝脏和胰腺缺血再灌注。在本研究中，我们探讨中性粒细胞来源的 MMP-9 在急性肠缺血再灌注中的作用及其与胰蛋白酶的相互作用。雄性Sprague-Dawley大鼠接受45分钟的肠系膜上动脉闭塞，随后进行90分钟的再灌注。近端空肠的原位酶谱显示缺血再灌注后肠壁中的明胶酶活性增加。凝胶电泳酶谱和免疫荧光共定位表明，这种明胶酶活性源自浸润中性粒细胞释放的 MMP-9。使用肠缺血再灌注的体内分离空肠环模型研究了腔内胰蛋白酶在此过程中的作用。胰蛋白酶增加了再灌注后的炎症反应，增加了肠壁的中性粒细胞浸润。此外，胰蛋白酶刺激中性粒细胞释放的 proMMP-9 快速转化为较低分子量的酶活性 MMP-9。这一过程代表了胰蛋白酶诱导的 MMP-9 激活的强大体内病理生理机制，并且可能在急性肠道炎症和休克的发展中发挥核心作用。
Ischeinia-reperfusion of the intestine produces a set of inflammatory mediators, the origin of which has recently been shown to involve pancreatic digestive enzymes. Matrix metalloproteinase-9 (MMP-9) participates in a variety of inflammatory processes including myocardial, hepatic, and pancreatic ischemia-reperfusion. In the present study, we explore the role of neutrophil-derived MMP-9 in acute intestinal ischemia-reperfusion and its interaction with pancreatic trypsin. Male Sprague-Dawley rats were subjected to 45 minutes of superior mesenteric arterial occlusion followed by 90 minutes of reperfusion. In situ zymography of the proximal jejunum reveals increased gelatinase activity in the intestinal wall after ischemia-reperfusion. Gel electrophoresis zymography and immunofluorescence co-localization suggests that this gelatinase activity is derived from MMP-9 released from infiltrating neutrophils. The role of intraluminal trypsin in this process was investigated using an in vivo isolated jejunal loop model of intestinal ischemia-reperfusion. Trypsin increased the inflammatory response after reperfusion, with an augmented neutrophil infiltration of the intestinal wall. Furthermore, trypsin stimulated a rapid conversion of neutrophil-released proMMP-9 into the lower molecular weight enzymatically active MMP-9. This process represents a powerful in vivo pathophysiological mechanism for trypsin-induced MMP-9 activation and is likely to play a central role in the development of acute intestinal inflammation and shock.