BACKGROUND:Toll-like receptor(TLR)2/4 might play important roles in mediating proinflammatory cytokine synthesis and release.And nitric oxide(NO)has been used to treat acute respiratory distress syndrome(ARDS).This st...BACKGROUND:Toll-like receptor(TLR)2/4 might play important roles in mediating proinflammatory cytokine synthesis and release.And nitric oxide(NO)has been used to treat acute respiratory distress syndrome(ARDS).This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury(ALI)complicated by acute hemorrhage necrotizing pancreatitis(AHNP)and the effect of NO on the TLR2/4 gene expression.METHODS:One hundred and ten SD male rats were randomly divided into sham-operated group(n=10),AHNP group(n=30),chloroquine-treated group(n=30),and L-Arg-treated group(n=40).The lungs were dissected for lung histological scoring,and bronchoalveolar lavages were harvested for lung injury indexing.TLR2/4 mRNA expression in the lungs was measured by RT-PCR.RESULTS:TLR2/4mRNA was detected in the lungs with low values in the sham-operated group(0.016±0.210E-2,0.112±0.750E-2),but it was markedly increased at 3 hours in the AHNP group(0.787±0.751E-2,1.512±1.794E-2),peaking at 12 hours(1.113±6.141E-2,2.957±2.620E-2;P<0.05 or P<0.01).When lung injuries were aggravated,TNF-αconcentrations in the lungs were increased,but NO concentrations were decreased(P<0.05 or P<0.01).When TLR2/4mRNA was inhibited by CQ(3h:0.313±5.491E-2,0.005±1.419E-3;6h:0.488±7.442E-2,0.010±1.518E-3;12h:0.883±8.911E-2,0.024±2.760E-3;P<0.05 or P<0.01),lung injuries were relieved.NO concentrations in the lungs were increased but TNF-αconcentrations were decreased(P<0.05 or P<0.01).When the rats with AHNP were treated with L-Arg,TLR2/4mRNA expression in the lungs could be effectively inhibited(50mg-T:0.656±3.977E-2,1.501±6.111E-2;100mg-T:0.260±0.891E-2,0.732±5.135E-2;200mg-T:0.126±0.914E-2,0.414±1.678E-2;400mg-T:0.091±0.399E-2,0.287±0.176E-2;P<0.05 or P<0.01)and lung injuries were relieved.At the same time,NO concentrations in the lungs were markedly increased,but TNF-αconcentrations were decreased(P<0.05 or P<0.01).CONCLUSIONS:The expression of TLR2/4mRNA is increased in the lungs in rats with AHNP and lung injuries are aggravated.TLR2/4mRNA gene expression of the lungs of rats with AHNP could be markedly inhibited by NO,leading to the relief of lung injuries.展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China (No. 30200272).
文摘BACKGROUND:Toll-like receptor(TLR)2/4 might play important roles in mediating proinflammatory cytokine synthesis and release.And nitric oxide(NO)has been used to treat acute respiratory distress syndrome(ARDS).This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury(ALI)complicated by acute hemorrhage necrotizing pancreatitis(AHNP)and the effect of NO on the TLR2/4 gene expression.METHODS:One hundred and ten SD male rats were randomly divided into sham-operated group(n=10),AHNP group(n=30),chloroquine-treated group(n=30),and L-Arg-treated group(n=40).The lungs were dissected for lung histological scoring,and bronchoalveolar lavages were harvested for lung injury indexing.TLR2/4 mRNA expression in the lungs was measured by RT-PCR.RESULTS:TLR2/4mRNA was detected in the lungs with low values in the sham-operated group(0.016±0.210E-2,0.112±0.750E-2),but it was markedly increased at 3 hours in the AHNP group(0.787±0.751E-2,1.512±1.794E-2),peaking at 12 hours(1.113±6.141E-2,2.957±2.620E-2;P<0.05 or P<0.01).When lung injuries were aggravated,TNF-αconcentrations in the lungs were increased,but NO concentrations were decreased(P<0.05 or P<0.01).When TLR2/4mRNA was inhibited by CQ(3h:0.313±5.491E-2,0.005±1.419E-3;6h:0.488±7.442E-2,0.010±1.518E-3;12h:0.883±8.911E-2,0.024±2.760E-3;P<0.05 or P<0.01),lung injuries were relieved.NO concentrations in the lungs were increased but TNF-αconcentrations were decreased(P<0.05 or P<0.01).When the rats with AHNP were treated with L-Arg,TLR2/4mRNA expression in the lungs could be effectively inhibited(50mg-T:0.656±3.977E-2,1.501±6.111E-2;100mg-T:0.260±0.891E-2,0.732±5.135E-2;200mg-T:0.126±0.914E-2,0.414±1.678E-2;400mg-T:0.091±0.399E-2,0.287±0.176E-2;P<0.05 or P<0.01)and lung injuries were relieved.At the same time,NO concentrations in the lungs were markedly increased,but TNF-αconcentrations were decreased(P<0.05 or P<0.01).CONCLUSIONS:The expression of TLR2/4mRNA is increased in the lungs in rats with AHNP and lung injuries are aggravated.TLR2/4mRNA gene expression of the lungs of rats with AHNP could be markedly inhibited by NO,leading to the relief of lung injuries.
