Experimental Study On Repairing Effect Of Keratinocyte Growth Factor-2 On Lung Injury Induced By Smoke Inhalation

Objective:To observe the effect of keratinocyte growth factor-2 on lung injury induced by smoke and to study its mechanism.Methods:120 in New Zealand white rabbits were made into smoke inhalation injury model and randomly divided into five groups: 0mg/kg Group:The injured rabbits were not treated;PBS group: After 4 hours of injury,the rabbits were induced by inhalation of phosphate buffered saline solution(PBS)5ml for a period of 1 days,for a period of 7 days;1mg/kg Group:At 4 hours after injury,the rabbits were inhaled KGF-2(1mg/K g,dissolved in 5ml PBS),once a day for 7 days;2mg / kg Group: At 4 hours after injury,the rabbits were inhaled KGF-2(2mg/K g,dissolved in 5ml PBS),once a day for 7 days;5mg/kg Group: At 4 hours after injury,the rabbits were inhaled KGF-2(5mg/K g,dissolved in 5ml PBS),once a day for 7 days;Each group was treated with 1d,3d,5d and 7d respectively,and the blood gas analysis was performed at different time points.the rabbits were sacrificed and the specimens were collected.The levels of Alveolar surfactant protein A(SP-A),vascular endothelial growth factor(VEGF)and Bcl-2 protein in lung tissue were measured by Western blot.Real time PCR was used to detect the mRNA of pulmonary surfactant protein A,vascular endothelial growth factor and Bcl-2 protein in lung tissue.The apoptosis was detected by TUNEL,and the pathological changes of lung tissue were observed.Results:(1)0mg/kg group vs PBS group,the PaO2 and PaCO2 had no significant difference between the two groups(P> 0.05);after injury,survival time had influence on PaO2 and PaCO2(P<0.01),with the prolongation of survival time,the overall changes of PaO2 and PaCO2 has an upward trend;Inhalation of KGF-2 had no significant effect on PaCO2 in rabbits with smoke inhalation injury(P>0.05),has an effect on PaO2(P < 0.01),the difference between 5mg/kg group and each group was significant(P<0.05),KGF-2 interacts with time(P<0.05),5mg/kg group,the most obvious increase in oxygen partial pressure at 7d.(2)0mg/kg group vs PBS group,the contents of SP-A,VEGF,Bcl-2 and their mRNA expression showed no significant difference in lung tissue of animal(P>0.05);after injury,survival time had influence on Bcl-2,SP-A,VEGF and their mRNA expression(P<0.01),with the prolongation of survival time,the overall changes of Bcl-2,SP-A,VEGF and their mRNA expression has an upward trend;The results showed that Bcl-2,SP-A,VEGF and their mRNA expression in lung tissue of injured animals were affected by inhalation of KGF-2(P<0.01).It can increase the content of Bcl-2,SP-A,VEGF and the expression of mRNA in lung tissue,5mg/kg group compared with other groups were significantly different(P<0.05),5mg/kg group,improve pulmonary Bcl-2,SP-A,VEGF content and mRN A expression is most obvious at 7d.(3)0mg/kg group vs PBS group,there was no significant difference in the apoptosis index of lung tissue(P>0.05).After the injury,the sur vival time has effect on the apoptosis index of lung tissue(P<0.01),with the prolongation of survival time,the overall change of the apoptosis index has an reduced trend;The effect of KGF-2 inhalation on apoptosis index of lung tissue was observed(P<0.01),can reduce the apoptosis index of lung tissue,There was significant difference between 5mg/kg group and each group(P<0.05),KGF-2 interacts with time(P<0.01),In 5mg/kg group,the apoptosis index of lung tissue was significantly decreased at 7d.(4)Pathological examination of lung tissue showed that compared with the first day after injury,the lung injury of seventh days in each group was lower than before.compared with each group,5mg/K g group of animals to reduce the most obvious damage.Conclusion:KGF-2 has a repair effect on lung injury induced by smoke inhalation.The repairing effect may be related to the mechanism of KGF-2 increasing the synthesis of pulmonary surfactant protein A,the promotion of pulmonary neovascularization,and the inhibition of apoptosis in lung injury.