| Part 1 Protective effect of sevoflurane pretreatment with different concentrations on lungs of rats with acute lung injury by lipopolysaccharideObjective:To investigate the effects of sevoflurane pretreatment with different concentrations on lung ICAM-1,CINC-1 mRNA and protein expression in rats with acute lung injury by lipopolysaccharideMethods:Forty-eight male SD rats anesthetized by intraperitoneal injection of 20%urethane 1g/kg which were tracheostomized and mechanically ventilated for 30 min were randomly divided into six groups,eight of each:(1) group A(control group);(2) group B(1.5MACSevo group);(3) group C(1.5MACSevo pretreatment group);(4) group D(1.0MACSevo pretreatment group);(5)group E(0.5MACSevo pretreatment group);(6) group F(LPS group),ventilated 30 minutes later,group F(LPS group) were vena femoralis injected with LPS 5mg/kg,group A(control group) were vena femoralis injected with lml/kg saline;group B(1.5MACSevo group) inhalated 1.5 MAC sevoflurane 30 minutes later,were vena femoralis injected with 1ml/kg saline;before injected with LPS 5mg/kg,group C,D and E were inhalated 1.5 MAC,1.0MAC and 0.5MAC sevoflurane for 30 minutes respectively.Blood pressure was measured directly from artery during above processes mentioned,mean arterial pressure and arterial blood gas were both measured and recorded at four time points T0(fight before inhalated sevoflurane),T1(right after inhalated sevoflurane),T2(2 hours after injection),T3(6 hours after injection).All groups were sacrifced respectively by losing blood at T3 time point.The dry/wet(D/W) ratio, the activity of myeloperoxidase(MPO) in lung tissues were determined and lung biopsies were also obtained.The expression of ICAM-1, CINC-1 mRNA and protein were detected in lung tissue.Results:(1)Compared to group A:W/D ratio in lung tissue of group C,D,E,F increased at different extent(P＜0.05),pathologic scores in lung of group C,D,E,F also increased(P＜0.05).Compared to group F: there were no obvious different of W/D ratio with group C,D,E (P＞0.05),but group E increased(P＜0.05);pathologic scores in lung of group C,D,E decreased(P＜0.05),and group D was the most obvious. There were no obvious pathologic changes in lung of group B(P＞0.05);(2)Compare to group A,MPO activity was increased in lung homogenates of group C,D,E,F(p＜0.05),moreover the expression of ICAM-1,CINC-1 mRNA and protein were increased in lung tissues of group C,D,E,F too(p＜0.05).Compared to group F,MPO activity and the expression of ICAM-1,CINC-1 mRNA and protein were decreased in group C,D,E(p＜0.05),especially in group C and D,the difference between group C and group D was not significant,while between group C D and E was siginificant(p＜0.05);(3) MPO activity and the expression of ICAM-1,CINC-1 mRNA and protein in group B were not obvious different from group A(p＞0.05).Conclusions:(1)Vena femoralis injected LPS 5mg/kg could induce ALI in rats. (2)Sevoflurane pre-treatment with different concentrations,especially 1.0MAC sevoflurane pre-treatment could decrease inflammatory reaction in ALI induced by LPS.Part 2 Expression and effect of HO-1 in lung tissues of lipopolysaccharide-induced ALI rats with sevoflurane pre-treatmentObjective:To investigate the effect of sevoflurane pretreatment with 1.0 MAC on lungs of rats with acute lung injury by lippolysaccharide,to observe the expression and significance of HO-1 mRNA,protein in lungs.Methods:Forty-eight male SD rats anesthetized by intraperitoneal injection of 20%urethane 1g/kg which were tracheostomized and mechanically ventilated for 20 min were randomly divided into six groups,eight of each,group A(control group),group B(ZnPP group), group C(1.0MACSevo group),group D(1.0MACSevo+LPS group),group E(ZnPP +1.0MACSevo+LPS group),group F(LPS group).rats in group B,E were vena femoralis injected 10mg/kg ZnPP, while 1mg/kg saline in other groups.Ten minutes later,rats in groupC,D,E inhalate 1.0 MAC sevoflurane for 30min,then groupD,E,F were vena femoralis injected LPS 5mg/kg,while 1mg/kg saline in other groups. All groups were sacrificed respectively by losing blood.The dry/wet (D/W) ratio,the activity of myeloperoxidase(MPO) and HO-1 in lung tissues were determined and lung biopsies were also obtained.The expression of ICAM-1,CINC-1,and HO-1 protein was detected by western-blotting while the expression of ICAM-1,CINC-1,and HO-1 mRNA was detected by RT-PCR in lung tissues.Results:(1) The D/W ratio,pathologic scores,the activity of MPO,HO-1 and the expression of ICAM-1,CINC-1,HO-1 mRNA and protein in rats of group B and C were not obviously different from that of group A(p＜0.05).(2) Compared to group A,the D/W ratio in rats of group D,E,F were significantly increased(p＜0.05).There were pathologic changes which manifested as the increase of pathologic scores in lung of group D,E,F.The pathologic changes were more slightly in group D than in group E,F,the differences were statically significant(p＜0.05).(3)Compare to group A,MPO activity were increased in lung homogenates of group D,E,F(p＜0.05),moreover the expression of ICAM-1,CINC-1 mRNA and protein were increased in lung tissues of group D,E,F too(p＜0.05).Compared to group E and F,MPO activity and the expression of ICAM-1,CINC-1 mRNA and protein were decreased in group D(p＜0.05).(4)The activity of HO-1,expression of HO-1 mRNA and protein in group F were higher than group A(p＜0.05),while these in group D were higher than group F(p＜0.05),the activity of HO-1,expression of HO-1 mRNA and protein in group E were lower than group D(p＜0.05).Conclusions:(1) HO-1 expression of the lung tissue have protective effect on LPS-induced ALI (2)The protective effect of sevoflurane pre-treatment on LPS-induced ALI were produced by uptaking of HO-1 expression.(2) The protective effect of sevoflurane pre-treatment on ALI could be eliminated by ZnPP which was the specific inhibitor of HO-1.
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