Pulmonary INOS And NO Production During LPS-initiated Lung Inflammation In Endotoxin Tolerance Rats

Objective: To study the pulmonary inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production of endotoxin tolerance rats in endotoxemia.Methods : Seventy-two Sprague-Dawley male male rats were randomized into endotoxin tolerance (ET) group and normal control (NC) group. Endotoxin tolerance was induced by intraperitoneal injection of 0.1 mg/kg Escherichia coli LPS (serotype 0127:B8) at the first day and intraperitoneal injection of 0.5mg/kg LPS on days 2-5. NC group received intraperitoneal injections of the same volume saline.72 hours after the last LPS injection, all rats were intraperitoneally injected with high dose of LPS (10 mg/kg) to induce endotoxemia and lung inflammation. Right lung tissue were collected before and 2,4,6,12,24 hours after the high dose injection of LPS (six rats for each time point).The production of pulmonary iNOS,NO,MPO and MDA were measured by Griess. The histological change of the left lung at the 6 and 12 hour were observed under light microscope. Software SPSS 13.0 was utilized for statistical analysis.Results: Before high dose LPS challenge, all the four variables in ET group were slightly elevated, but did not reach statistical meaning compared with NC group. In NC group ,the level of four variables were respectively significantly increased from 4 hours to 12 hours after challenge. As contrasted, the four variables were increased a little in ET group. Under the light microscope, the pathologic change induced by high dose of LPS were significantly attenuated in the ET group. Conclusions: The induction of rat endotoxin tolerance is associated with a profoundly low level of iNOS,NO,MPO and MDA production in lung tissue when they are challenged with high dose LPS.