25. THE ROLE OF DIGESTIVE ENZYMES IN INTESTINAL PERMEABILITY AFTER ISCHEMIC SHOCK

Department: Bioengineering
Faculty Advisor(s): Geert Schmid-Schönbein

Primary Student
Name: Marisol Chang
Email: m8chang@ucsd.edu
Phone: 817-917-6110
Grad Year: 2011

Abstract
Shock is a devastating clinical problem which causes high patient mortality; the intestinal lumen is the most vulnerable organ to shock injury due to ischemia. It has been shown that triggers of shock may cause an increased permeability of the intestinal mucosal layer leading to inflammation and necrosis of the gastrointestinal tract. The end result of these events is the leakage of inflammatory mediators out of the intestinal lumen causing cellular dysfunction, multiple organ failure and subsequently death. However, the mechanisms by which these events take place it is still not fully understood; digestive enzymes and their products located in the lumen of the intestine are the major candidates to mediate the inflammation and necrosis in shock. There is now substantial evidence that tight junctions play a major role in regulating epithelial permeability by influencing paracellular flow, thus making them the major target during intestinal ischemia. It is hypothesized that digestive enzymes play a significant role in the opening of the paracellular seal by disruption of the tight junctions. The objective of the proposed study is to unravel the mechanism responsible for the damage of the intestinal wall by understanding the direct effect of digestive enzyme in tight junction disruption.

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