The Role Of Macrophage Inflammatory Protein-1α And Nuclear Factor-κB In The Ventilator Induced Lung Injury In Rats

Objective To evaluate the role of macrophage inflammatory protein-1a (MIP-1a) and nuclear factor-?B (NF-?B) in the ventilator induced lung injury by observing the expression of MIP-1a and NF-?B in the rats ventilated with different tidal volume. Methods Thirty-two normal Wistar rats were randomly divided into four groups: Control group,Low tidal volume group,Conventional tidal volume group and High tidal volume group. Then the pathologic changes of the lungs of each group were observed under macroscopy, light and electronic microscope, and the number of white blood cells(WBC) and the neutrophils in bronchoalveolar lavage fluid (BALF) was calculated .And the activities of myeloperoxidase (MPO) in BALF and plasma were measured with biologic method.Then the expressions of MIP-1a and NF-?B protein on pulmonary bronchiole epithelial cells, alveolar epithelial cells and alveolar macrophages from BALF were measured with immunohistochemistry stain respectively .The content of MIP-1a in plasma and BALF were measured with ELISA .In addition, expression of MIP-1a mRNA was investigated with in situ hybridization . Results 1 Different levels of interstitial and alveolar edema , the infiltration and activation of inflammation cells could be seen in the high tidal volume group and the conventional tidal volume group. There were no obvious pathologic differences between the low tidal volume group and the control group. 2 The WBC and neutrophils count in BALF were significantly higher in rats ventilated with high tidal volume and conventional tidal volume than in those ventilated with low tidal volume and control group(P<0.001);there were no statistical difference between the last two groups(P>0.05). 3 MPO activities in BALF were significantly higher in rats ventilated with high tidal volume and conventional tidal volume than in those ventilated with low tidal volume and control group (P<0.01,P<0.05), but no statistical difference could be found between low tidal volume group and control group (P>0.05).And there were no difference in MPO activities in plasma among the four groups (P>0.05). 4 The contents of MIP-1a in BALF in the high tidal volume group and the conventional tidal volume group were significantly increased as compared with the control group and the low tidal volume group (P<0.01). 5 Expressions of MIP-1a protein in pulmonary bronchiole epithelial cells, alveolar epithelial cells and alveolar macrophages from BALF in the high and the conventional tidal volume group were increased distinctly compared with the control group and the low tidal volume group (P<0.05). 6 The levels of NF-?B in nucleus of bronchiole epithelial cells and alveolar macrophages from BALF in the high and the conventional tidal volume group were higher than those in the control group and the low tidal volume group (P<0.05) 7 Expressions of MIP-1a mRNA in pulmonary bronchiole epithelial cells in the high and the conventional tidal volume group were obviously higher than those in the control group and the low tidal volume group (P<0.05). 8 The percentage of NF-?B nuclear staining positive cells correlated with the level of MIP-1a protein in the bronchiole epithelial cells and the macrophages from BALF in rats with lung injury.(r=0.552,0.522,P<0.05). Conclusion: 1. The pathologic changes of lung injury induced by the ventilator were different levels of interstitial and alveolar edema , the infiltration and activation of inflammation cells, and the injury was not limited in the alveolar , the bronchiole epithelial cells also could be effected. 2. Alveolar macrophage plays an important role in the ventilator induced lung injury by activating and expressing inflammatory factor:MIP-1a. 3. Nuclear factor –?B may take part in the process of lung injury induced by mechanical ventilation by modulating the expression of MIP-1a.