Ulinastatin attenuates lung ischemia-reperfusion injury in rats by inhibiting tumor necrosis factor alpha.

Abstract

UNLABELLED: Ischemia-reperfusion (I/R) injury may influence graft function following transplantation. Ulinastatin, a urinary trypsin inhibitor has been shown to attenuate I/R injury in various organs such as intestine, heart, and kidney in animals. The present experiment was designed to evaluate the effect of pretreatment with ulinastatin on I/R-induced lung injury. METHODS: After establishing a constant left lung warm ischemia-reperfusion model in rats, 45 animals were randomly divided into three experimental groups: sham group (n = 15), IR group (n = 15), and ulinastatin (5000 U/kg pre-ischemia) + IR group (n = 15). The lung injury was evaluated by tissue myeloperoxidase activity, with simultaneous estimation of the serum concentration of TNFalpha. RESULTS: The ulinastatin-pretreated animals exhibited markedly decreased lung tissue myeloperoxidase activity (P < .05). Blood gas analysis demonstrated, that the treated animals had significantly ameliorated pulmonary oxygenation (P < .05). The serum concentration of TNF-alpha in the ulinastatin-pretreated group was markedly decreased compared with that of the I/R group (P < .05). CONCLUSIONS: Ulinastatin attenuated I/R-induced lung injury. This function is partly related to the capacity of the agent to inhibit myeloperoxidase activity in lung tissue and decrease systemic expression to TNF-alpha.