Effects Of Inhaling Recombinant Human Keratinocyte Growth Factor-2 On The Oxygen Cooperation And Inflammatory Response Induced Bysmokein Halation Injury In Rabbits

Objective:To investigate the effects of recombinant human keratinocyte growth factor-2 on the inflammatory response induced by smoke inhalation injury in rabbits.Methods:120 New Zealand white rabbits were randomly divided into five groups.There were 24 rabbits in each group?n = 24?.O ne group of animals ate and drank normally after smoke inhalation injury,for the control group;since 1 day after injury,every day the other groups respectively inhaled 5ml PBS or 5ml PBS with 1mg/kg,2mg/kg,5mg/kg recombinant human keratinocyte growth factor-2,for the experimental groups.One day after atomization treatment 1 times,3 times,5 times and 7 times after anesthesia,each group separately took 6 animals to carry on arterial blood gas analysis,testing heart blood inflammatory markers IL-6,IL-8,IL-10 and MCP-1 level.PBS buffer was used to wash the left lung and the levels of IL-6,IL-8,IL-10 and MCP-1 in bronchoalveolar lavage fluid were measured.The lower lobe of right lung was examined by histopathology.Results:1.The integral analysis results of PaO₂,SaO₂ indicated that the drug factor had a significant effect?P<0.001?.The results of multiple comparisons within groups of PaO₂,SaO₂ showed that 1mg group,2mg group and 5mg group showed significant differences?P<0.05?when compared with PBS group and 5mg vs 1mg had marked differences in index PaO₂.The time factor had a obvious role in the integral analysis of PH,PaO₂,PaCO₂,SaO₂ and HCO₃^-,the P<0.001 in index PH,PaO₂,PaCO₂,SaO₂,the P<0.05 in index HCO₃^-.The results of multiple comparisons within groups of PH,PaO₂,SaO₂ showed that 3d vs 1d,5d vs 1d and 7d vs 1d were significantly different?P<0.05?.7d vs 3d of PH were remarkably different?P<0.05?;3d vs 1d,5d vs 1d of PaCO₂ had significant differences?P<0.05?;5d vs 1d in the HCO₃^-had a significant difference?P<0.05?.2.Pathological examinations of each animal showed the alveolar cavity had varying degrees of inflammatory exudation and hemorrhage,cystic dilatation or part of alveolar collapse,bro nchial mucosa appeared different degrees of degeneration and necrosis,inflammatory exudate cavity adhesion.With the change of time,neutrophil infiltration,exudation and hemorrhage in alveolar cavity and interstitial space were gradually reduced.After injury 5d or 7d,the above changes were most significant in 5mg group.3.The integral analysis results of IL-6,IL-8 and IL-10 in the bronchoalveolar lavage fluid?BALF?revealed that the drug and time had a significant effect?P<0.05?At the dose level,the results of multiple comparisons within groups of IL-6 showed that 2mg group vs PBS group and 5mg group vs PBS group had a significant difference?P<0.05?;the results of multiple comparisons within groups of IL-8 showed that 1mg group vs PBS group,2mg group vs PBS group and 5mg group vs PBS group were very different?P<0.05?;the results of multiple comparisons within groups of IL-10 showed that there was a difference between 1mg group and 2mg group?P<0.05?.At the time level,the results of multiple comparisons within groups of IL-6 showed that 7d vs 1d had a remarkable difference?P<0.01?;the results of multiple comparisons within groups of IL-8 showed that 5d vs 1d,7d vs 1d and 7d vs 3d had significant differences?P<0.05?;the results of multiple comparisons within groups of IL-10 showed that 3d vs 1d and 7d vs 3d had significant differences?P<0.05?.There was no significant difference in the result of MCP-1 in bronchoalveolar lavage fluid?P>0.05?.4.The analysis results of the inflammatory markers in serum revealed that the drug showed no significant effect.IL-6 was not detected in nearly half of the serum samples.The time factor had a significant role in the integral analysis of IL-8 and IL-10 in serum?P<0.05?.The results of multiple comparisons within groups of IL-8 in serum showed that 5d vs 1d,7d vs 1d had a significant difference?P<0.01?and that 7d vs 3d had a difference?P<0.05?.The results of multiple comparisons within groups of IL-10 in serum showed that 7d vs 1d had a significant difference?P<0.05?.There was no significant difference in the result of MCP-1 in serum?P>0.05?.Conclusion: Inhalation of rhKGF-2 to treat smoke inhalation injury could significantly improve the oxygen cooperation and reduce the degree of inflammation reaction of lung tissue injury after smoke inhalation,with no significant effect on systemic inflammatory reaction.