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Trypsin and MMP‐9 Levels and Activity Increase in Plasma, Peritoneal Space, and Vital Organs during Hemorrhagic Shock
Author(s) -
Altshuler Angelina E,
Penn Alexander H,
Yang Jessica,
Kim Ga-Ram,
Schmid-Schonbein Geert W
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1132.1
Subject(s) - trypsin , pancreas , peritoneal fluid , zymography , proteases , medicine , endocrinology , protease , chemistry , matrix metalloproteinase , enzyme , biochemistry
Hemorrhagic shock (HS) is a major cause of death after trauma. During HS, perfusion to the intestine and pancreas are reduced, resulting in increased intestinal mucosal permeability, pancreatitis, and potential leakage of serine proteases (i.e. trypsin‐a potent matrix metalloproteinase [MMP] activator) into the circulation. We hypothesize that after HS, both trypsin and MMP‐9 enter the circulation, peritoneal space, and appear in peripheral organs. Male Wistar rats were grouped into No‐HS or HS (N=5). Mean arterial blood pressure of HS animals was reduced to 35 mmHg (2 hr) followed by resuscitation of shed blood (2 hr). Plasma and peritoneal lavage fluid were obtained before and after HS. The heart, lung, liver, and brain were collected. Protease activities in plasma and peritoneal fluid were measured by plate zymography (trypsin‐like and MMP‐9 specific substrates) or gelatin gel zymography. Pancreatic trypsin and MMP‐9 levels were identified by immunoblot. Trypsin‐like activities were elevated in plasma and peritoneal space fluid after HS (p<0.05). Immunoblot for pancreatic trypsin detected elevated levels in the plasma, peritoneal fluid, and lungs. MMP‐9 activity and protein levels were elevated in all compartments after HS (p<0.05). In HS, trypsin may be transported from the permeable intestine and/or pancreas into the periphery and may contribute to MMP‐9 activation.