| Objective: Thrombolysis therapy of pulmonary embolism (PE) may cause reperfusion injury, the mechanism of which is still unclear. Nitric oxide(NO) is an bioinformational and effector molecule which has been well investigated for the past few years. Nuclear factor (NF)-κB is a fast response transcription factor which has multipetal regulating fuction. NF-κB can specifically bind withκB sites in promoter site of various genes. In recent years, a lot of works are done and found that NF-κB can regulate the production of NO, and play a part in pulmonary E/R, but the mechanism is still unclear. We established the New Zealand rabbit animal model to observe the effect of NF-κB in the change of NO,NOS in the pulmonary E/R injury, and investigate the possible mechanism of lung embolism/ reperfusion injury.Methods: The New Zealand big ear white rabbits were used in this experiment. First the left lower lung artery were obstructed by Berman catheter, then the balloon was deflated to restore blood flow to allow reperfusion, in order to establish the acute rabbit lung embolism/reperfusion injury model. The mor- phological changes, the dynamic changes of the NO, the NOS, the MDA, the SOD in the lung tisse homogenate and the BALF were observed. Immunohistochemistry was used to detect the expression of NF-κBp65 in the lung tissue during the pulmonary embolism.Results: (1) Llight microscope showed endothelial cell swelling, alveolar wall hyperaemia, lots of inflammatory cells infiltrating, lung consolidation after lung embolism/reperfusion. (2) Changes of MDA: Compared with control group, the lung tisse homogenate MDA was increased at lung embolism 2h, and was continuously increased at reperfusion 1h, and reached the peak value at reperfusion 2h(0.68±0.05, 0.72±0.09, 0.84±0.07). The lung tissue homogenate MDA in reperfusion 2h group was higher than in reperfusion 1h group (P<0.05), it was signifycantly higher than embolism 2h group (P<0.05). The changes of MDA in BALF was similar to the changes in the lung tisse homogenate. (3) Changes of SOD: Compared with control group, the lung tissue homogenate SOD was decreased at lung embolism 2h, further decreased at reperfusion 1h, and the decrease was most obvious at reperfusion 2h(418.66±78.93, 326.63±59.01, 253.81±35.12, P<0.05). The lung tissue homo- genate SOD in reperfusion 2h group was higher than in reperfusion 1h group (P<0.05). The SOD change tendency in BALF was also similar to that in the lung tissue homogenate. (4) Changes of NO: Compared with control group, the lung tisse homogenate NO was increased at lung embolism 2h, and was continuously increased at reperfusion 1h, and reached the peak value at reperfusion 2h(2.24±0.38, 2.83±0.63, 4.26±0.83). The lung tissue homogenate NO in reperfusion 2h group was higher than in reperfusion 1h group (P<0.05), it was significantly higher than embolism 2h group(P<0.05). The changes of NO in BALF was similar to the changes in the lung tisse homogenate. (5) Changes of NOS: Compared with control group, the lung tisse homogenate iNOS was increased at lung embolism 2h, and was continuously increased at reperfusion 1h, and reached the peak value at reperfusion 2h(56.70±8.04, 70.35±6.36, 100.65±12.15). The lung tissue homogenate iNOS in reperfusion 2h group was higher than in reperfusion 1h group (P<0.05), it was significantly higher than embolism 2h group (P<0.05). There is no obvious change in the lung tissue homogenate cNOS in control group, sham group and various treatment groups (566.18±65.12, 563.20±85.93, 588.52±79.09, 539.50±73.81, 537.99±64.33, P>0.05). (6) After the lung embolism/reperfusion, immunohistochemistry demonstrated that the massive expre- ssions of NF-κBp65 positive cell in rabbit lung tissue were mainly located in pulmonary alveolus epithelial cells, partly small vascular endothelial cells and inflammatory cells (mononuclear cell, granular leukocytes). Compared with sham group, the relative amount of NF-κBp65 was increased at embolism 2h, and reperfusion 1h, 2h(P<0.01). (7) Linear regretssion analysis showed that the NF-κBp65 expression level was significantly correlated with lung tissue NO and iNOS content, BALF NO (r=-0.569, -0.510, -0.565, all P<0.05). The lung tissue and BALF NO content were significantly correlated with lung tissue iNOS content(r=0.883, 0.750, all P<0.01), but did not correlated with the lung tissue cNOS(P>0.05). The lung tissue and BALF NO content were significantly correlated with the MDA, SOD content in the lung tissue and BALF (all P<0.01).Conclusion: (1) In our experiment, we successfully established lung embolism/reperfusion animal model by using Berman balloon catheter. (2) The result of HE staining and MDA,SOD content of the lung show that the oxidizing reaction caused by lung embolism/reperfusion could lead to lung injury. (3) The expression levels of NF-κBp65 and iNOS were up-regulated in the processes of lung embolism and reperfusion, and NO was producted in large quantities. (4) Our experiment indicated that one of possible mechanisms for acute pulmonary embolism/reperfusion injury was that activated NF-κB regulated the expression of iNOS, which resulted in overexpression of NO, leading to acute pulmonary injury.
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