Effects Of Glucocorticoid On Inflammation And Coagulation Disorders In Smoke Inhalation Induced Acute Lung Injury In Rats

Objective Smoke inhalation induced acute lung injury(SI-ALI),with high mortality and morbility,is a common respiratory injury in fire disaster,and therapeutic strategy is still limited.Glucocorticoid,the potent immunoregulator,is controversial in SI-ALI management and the impact on coagulation system.In this study,we aimed to explore the changes of systemic and local inflammation and coagulation disorders caused by SI-ALI in rats model and explore the effects of diflerent dosages of methylprednlsolone(MP)on survival rates of SI-ALI,as well as the functions on inflammation and coagulation.Methods1.Establishment of SI-ALI Rat Model Adult male Sprague-Dawley(SD)rats were exposed to smoke generated by composite material-which were common in fire disaster-in self-made temperature-controlled smoke generator.Composition and concentration of smoke were monitored during combustion.Survivals of different inhalation groups were recorded.Local and systemic inflammation disorders were monitored,as well as hepatic-renal function.2.Accessment of Local and Systemic Coagulation in SI-ALI After smoke inhalation for 30 min,the trends of local and systemic coagulation factors,including factor Ⅱ(F Ⅱ),thrombin antithrombin complex(TAT-c),Ca2+,F V,F Ⅷ%,and anti-coagulation factors thrombomodulin(TM),antithrombin Ⅲ(AT Ⅲ),protein C%(PC%)were tested in 1,6,24 h.3.Effects of MP on Inflammation and Coagulation Disorders in SI-ALI After model establishment,3 different dosages of MP(40,4,0.4mg/kg),according to previous studies,were administrated 1 h before injury,aiming to explore the effects of glucocorticoid on 24 h survivals,coagulation and inflammation of SI-ALI.Results1.The survival rates at different inhalation periods were 84.21%(15 min),25%(30 min),0(50 min).There was a significant increase in carboxyhemoglobin(COHB),lactate(Lac),and PaCO2,as well as lung injury score(LIS),protein concentration in bronchoalveolar lavage fluid(BALF)at 1 h post 30 min smoke inhalation(P<0.05).In BALF,the total number of white cells significantly increased after smoke inhalation,while the proportion of macrophages significantly decreased at 6 h,then slightly recovered at 24 h;neutrophils showed the opposite trend.There was a significant increase in signal pathway factors and inflarmatory factors at 1 h recovery.2.There was a gradually decrease of F Ⅱ and increase of TAT-c in BALF after SI,while anti-coagulation factor TM sharply decreased in 1 h post 30 min smoke inhalation(P<0.01),which was significantly correlated with lung injury score(P<0.001).In peripheral blood,anti-coagulation factors,AT Ⅲ and PC%were markedly impaired in lh after SI,while TM was gradually increased.Pro-coagulation factors,Ca2+,F Vr F Ⅷ%demonstrated continuing decrease in blood.3.In our following study,we found different dosages of MP could improve survival rates after SI,while 4mg/kg MP functioned better than 40 and 0.4mg/kg.Both 40 and 4mg/kg MP could attenuate IL-17a and IL-6 levels in BALF and plasma(P<0.05),while 4 mg/kg MP brought more significant improvement in LIS compared with 40 mg/kg MP group.Western blot showed that all MP groups could attenuate the expressions of Myeloperoxidase(MPO),high mobility group box 1(HMGBI)in lung tissues,4mg/kg worked better than 40 and 0.4mg/kg.4 and 40mg/kg MP could in prove local pro-and anti-coagulation disorders in BALF caused by SI,especially in TF and TM mRNA improvement.While MP treatment could increase F Ⅷ and TF levels in plasma TAT-c was considerably decreased by 4 and 40mg/kg MP.Levels of anti-coagulation factors,including soluble TM and endothelial cell protein C receptor and PC%were markedly improved by 4mg/kg MP.Conclusions In this study,we established a steady isolated SI-ALI model with temperature control device.We found that SI-ALI was characterized by pro-inflammation and coagulopathy with significant consumption of pro-and anti-coagulation factors locally and systemically.TM in BALF reflected the severity of lung injury.High and medium dosages of MP could significantly attenuate inflammation and coagulation disorders in SI-ALI,while medium dosage demonstrated more efficient survival benefit.