Urinary trypsin inhibitor treatment ameliorates acute lung and liver injury resulting from sepsis in a rat model

OBJECTIVE: To evaluate the protective effect of urinary trypsin inhibitor (UTI) on acute lung and liver injury in rat model induced by sepsis with infra-abdominal infection. METHODS: This study was performed in the University of Wuhan, Wuhan, China in May 2007. Sepsis models were made by cecal ligation and puncture (CLP) in Sprague-Dawley rats. Forty rats were randomly divided into sham, CLP, CLP/UTI I (20 u/g) and CLP/UTI II (50 u/g) groups, with 10 rats in each. All of them were sacrificed 12 hours after CLP. The mean arterial pressure (MAP), heart rate (HR), the wet-to-dry lung weight ratio (W/D) was measured and venous blood was collected for assaying tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic acid. Superoxide dismutase (SOD), malondialdehyde (MDA) and expression of inducible nitric oxide synthase (iNOS) mRNA in lung and hepatic tissues were examined. RESULTS: Compared with the CLP group, MAP and HR in 50 u/g UTI treated rats was stable (p<0.01). Marked elevation levels of W/D ratio were lowered after administration of 50 u/g UTI (p<0.01). Treatment with 50 u/g UTI prevented marked elevation in MDA, ALT, AST, TNF-alpha, lactic acid levels, expression of iNOS mRNA, and elevated IL-10 and SOD activity (p<0.01). CONCLUSION: Urinary trypsin inhibitor has a protective effect against sepsis. Its action mechanisms are probably involved in the inhibition of inflammatory factor production and suppression of lipid peroxidation and iNOS mRNA expression.