| Background:Sepsis is the systemic inflammatory response syndrome caused by infection, the most common target organ is the lung, causing acute lung injury/acute respiratory distress syndrome. Severe sepsis, septic shock, reducing systemic organ blood flow and oxygen supply can lead to multiple organ dysfunction syndrome, with high morbility and mortality in ICU patients. Ulinastatin(UTI), as a urinary trypsin inhibitor, which can inhibit protease activity, eliminate inflammatory factors, scavenge oxygen free radicals, are commonly used in acute pancreatitis or severe infection to control excessive amplification of the inflammatory response and reduce organ damage. Heme oxygenase-1(HO-1) is the rate-limiting enzyme in the process of heme catabolism. Whether UTI can affect HO-1and induced nitric oxide synthase(iNOS) expression in lungs of septic rats is not clear.Objective:To investigate the changes of HO-1and iNOS in early lungs of septic rats, and the mechanisms of UTI protection.Methods:Male Wistar rats were randomly divided into three groups, the sham group, the sepsis group and the UTI group. Cecal ligation and puncture (CLP) method was used to establish the model of sepsis. After CLP, rats in UTI group was given UTI5million U/kg intravenous after Oh and12h of operation, while the same volume of saline was given to sepsis group. Rats were killed and specimens were taken from the lung tissue, at6h,12h,24h after CLP respectively. HE staining was done to show the pathological changes. HO-1and iNOS protein expression were shown by the application of immunohistochemical staining and Western blot. HO-1and iNOS mRNA were detected through Realtime PCR. Results:①From HE staining of the lung tissue of rats, sepsis group and the UTI group showed obvious tissue swelling, alveolar septal thicken, inflammatory cell infiltration, and even atelectasis compared with the sham group. The changes in sepsis group were obvious with time going on after CLP, while at the same time point, subgroups of the UTI group showed less pathological changes of rat lungs than the sepsis group.②Immunohistochemical analysis of HO-1and iNOS protein showed that, proteins at each time point of sepsis group were significantly higher than those of sham group, but the UTI group were lower than sepsis group.③By the western blot analysis of HO-1protein expression, the results were in accord with the immunohistochemical analysis. However,iNOS protein differences were only seen in24h group.④Compared with the sham group, HO-1mRNA level significantly increased at6h,12h and24h subgroups of sepsis group(1.7277±0.42073,1.7998±0.38334,1.7820±0.44001) while HO-1mNRA level of UTI group decreased significantly compared with the sepsis group(1.1013±0.25486,1.2612±0.30818,1.0995±0.25727)(F=19.262,20.626,20.924, P<0.05).At each time point of sepsis group, iNOS mRNA level were significantly higher than the sham group (4.3964±3.78825,5.0171±0.71085,4.3331±1.19443).There was no differences of iNOS mRNA expression at6h,12h between UTI group and sepsis group, while at24h subgroup of UTI, iNOS mRNA level(2.0500±.32206)was less than that of sepsis group (F=64.640, P<0.05).Conclusion:In rats, sepsis could induce acute lung injury by the production of HO-1and iNOS. UTI could inhibit the release of proinflammatory factors and alleviate oxidative stress, thereby reduce the expression of HO-1,iNOS and lung injury of septic rats. |
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