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The journal of trauma and acute care surgery

Inhibiting tryptase after ischemia limits small intestinal ischemia-reperfusion injury through protease-activated receptor 2 in rats.


PMID 22976423

Abstract

Mast cell activation plays a key role in the process of small intestinal ischemia-reperfusion (IIR) injury; however, the precise role of tryptase released from mast cell on IIR injury remains poorly understood. The aim of this study was to determine the protective role against IIR injury by using tryptase inhibitor protamine after ischemia and to explore the underlying mechanism. Adult Sprague-Dawley rats were randomized into sham-operated group (S), sole IIR group (IIR) in which rats were subjected to 75-minute superior mesenteric artery occlusion followed by 4-hour reperfusion, or IIR being respectively treated with mast cell stabilizer cromolyn sodium (CS group), with the mast cell degranulator compound 48/80 (CP group), or with protamine (P group). The previously mentioned agents were, respectively, administered intravenously 5 minutes before reperfusion. The intestine tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7 and protease-activated receptor 2 (PAR-2). The intestine mast cell number and levels of tumor necrosis factor κ and interleukin 8 were quantified. IIR resulted in intestinal injury evidenced as significant increases in Chiu's scores, accompanied with concomitant increases of mast cell counts and intestinal tryptase and mast cell protease 7 protein expressions. IIR also increased intestinal PAR-2 expressions, tumor necrosis factor κ, and interleukin 8 levels. Cromolyn sodium and protamine significantly reduced the responses to IIR injury while compound 48/80 further aggravated the previously mentioned biochemical changes. Tryptase releasing from mast cell activation participates in IIR injury through PAR-2, and inhibiting tryptase after ischemia provides promising benefits in limiting IIR injury.

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C0399
Cromolyn sodium salt, ≥95%
C23H14Na2O11