The Effects And Mechanisms Of Propofol And Ischemic Preconditioning On Lung Cell Apoptosis In Ischemia-reperfusion Injury Of Rats Lung

Objective To oberserve the effects of propofol,ischemic preconditioning and propofol combined with ischemic preconditioning on lung cell apoptosis in ischemia-reperfusion injury of rats lung.To investigate they possible mechanisms against ischemia-reperfusion injury.Methods Sixty healthy male SD rats weighing 220-250g were randomly divided into six groups as follows:(1)Sham group(n=10,suture was only placed in hilum of right lung without ischemia).(2)Ischemia group(n=10,only ischemia without reperfusion).(3)IR group(n=10, lung ischemia was produced by clamping the right lung hilum for 1h and then reperfusion for 2h.(4)Propofol group(n=10,propofol was infused starting from 30 min before ischemia,the other operation progress were same to IR group).(5)IP group(n=10,the hlium of right lung was blocked for five minutes and reopened for five minutes before ischemia.Above operation was repeated three times,the other operation were same to IR group).(6)Propofol+IP group(n=10, propofol was infused combining with Ischemic preconditioning starting from 30 min before ischemia Propofol).We use the rat model of warm ischemia and repefusion in situ in single lung. At the end of the experiment,all rats were killed to sample the lung tissue.The wet/dry ratio of lung tissue and were detected as index of the lung injury.Electron microscopy was performed to verify the morphologic changes of apoptosis.In the terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)method was used to detect lung cell apoptosis.Bax,Bcl-2 expression in lung tissue were analyzed by immunohistochemistry.Results There were no significant apoptosis changes in Sham group.There was a slight but no statistically significant elevation of apoptotic pneumocytes number in IS group compared with Sham group.Obvious apoptosis of pneumocytes occurred on 2h after reperfusion.AI were significantly higher in IR,Pro,IP and Pro+IPgroup than in Sham group(P＜0.01),but were significantly lower in Pro,IP and Pro+IPgroup than in IR group(P＜0.01).The expression of Bcl-2 and Bax was increased in IR group than in Sham group(P＜0.01),with a prominent decrease in the ratio of Bcl-2/Bax(P＜0.01).Compared with IR group,IP and Pro+IPgroup showed decreased expression of Bax(P＜0.05),but Pro group was no significant difference in the expression of Bax(P＞0.05).The expression of Bcl-2 and the ratio of Bcl-2/Bax were significantly higher in Pro,IP and Pro+IPgroup than in IR group(P＜0.01 or P＜0.05).There were no significant difference in IS group than in Sham group.There was a significant positive correlation between W/D and AI(r=0.951,P＜0.01),and there was a significant negative correlation between AI and the ratio of Bcl-2/Bax(r=-0.851,P＜0.01).Conclusions Compared with Sham group,the result indicates that the activation of Bax, Bcl-2 gene and its initiating cell apoptosis of lung tissues may contribute to the pathogenesis of lung ischemia-reperfusion injury.The ratio of Bcl-2/Bax declines gradually,which may play an important role on the occurrence of apoptosis.Propofol,IP can inhibit apoptosis in lung tissues and ameliorate pulmonary IR injury;the protective effects may include down-regulating on Bax expression or up-regulating on Bcl-2 expression in lung.The protective effect was strengthened when propofol and IP were used in combination.