Role of using two-route ulinastatin injection to alleviate intestinal injury in septic rats

Purpose: Early application of protease inhibitors through the intestinal lumen could increase survival following experimental shock by blocking the pancreatic digestive enzymes. Hence, it was hypothesized that two-route injection(intraintestinal + intravenous) of ulinastatin(UTI), a broad-spectrum protease inhibitor, could better alleviate intestinal injury than single-route injection(either intravenous or intraintestinal).Methods: A sepsis model induced by lipopolysaccharide on rats was established. The rats were randomly divided into five groups: sham, sepsis, UTI intravenous injection(Uiv), UTI intraintestinal injection(Uii),and UTI intraintestinal + intravenous injection(Uii + Uiv) groups. The mucosal barrier function, enzymeblocking effect, levels of systemic inflammatory cytokines, and 5-day survival rate were compared among groups. The small intestinal villus height(VH), crypt depth(CD), and two components of mucosal barrier(E-cadherin and mucin-2) were measured to evaluate the mucosal barrier function. The levels of trypsin and neutrophil elastase(NE) in the intestine, serum, and vital organs were measured to determine the enzyme-blocking effect.Results: Compared with the single-route injection group(Uiv or Uii), the two-route injection(Uii + Uiv)group displayed:(1) significantly higher levels of VH, VH/CD, E-cadherin, and mucin-2;(2) decreased trypsin and NE levels in intestine, plasma, and vital organs;(3) reduced systemic inflammatory cytokine levels; and(4) improved survival of septic rats.Conclusion: Two-route UTI injection was superior to single-route injection in terms of alleviating intestinal injury, which might be explained by extensive blockade of proteases through different ways.