Study On Lipopolysaccharide-induced Acute Respiratory Distress Syndrome And Protective Effects Of Curcumin In Rabbits

Objective:ARDS models of rabbits were reproduced with intravascular injection of lipopolysaccharide(LPS) in this study. By observing pathophysiological changes of ARDS models, the possible pathogenic mechanisms such as inflammatory mediators, oxidative stress and coagulation-fibrinolysis system disequilibrium were further studied. Furthermore, the effect of curcumin on LPS-induced ARDS in rabbits was investigated, and its possible mechanisms were explored.Methods:Twenty eight NewZealandwhite rabbits were randomly assigned to four groups:control group(C),model group(M), model+vehicle group(V) and treatment group(T).All rabbits were anaesthetized with 25% ethyl carbamate (3ml/kg) by intraperitoneal injection. Then separation of left common carotid artery and intubation were used for monitoring vital signs and collecting blood samples. ARDS models were replicated with intravascular LPS(720μg/kg) injection at a time in group M,V and T. Meanwhile curcumin(0.8ml/kg) was intraperitoneally injected as therapeutic method in group T. Group V was intraperitoneally injected with same dimethylsulfoxide(DMSO). In the course of the experiment, blood pressure, respiratory rate and arterial blood gas were measured at 0h,0.5h,2h,4h and 6h;contents of IL-17,IL-22 in serum and PAI-1 in plasma were detected at 0h,2h,4h and 6h respectively. Contents of IL-17,IL-22 in bronchoalveolar lavage fluid(BALF) and lung homogenate, activities of SOD,MPO and PAI-1 in lung homogenate, the wet-to-dry weigh ratio of lung tissue were also detected after animals were killed at 6h.Pulmonary histopathological changes were observed with optical microscope.Results:1. Respiratory rate(RR) and blood pressure(BP):During the experiment, RR in group C remained relatively stable, and BP showed a trend of slow decrease. After injecting LPS,RR in group M and group V significantly increased, and BP was significantly lower than group C(P<0.01).RR of Group T accelerated and BP declined, but the trends were less than model group (p< 0.01).2. Blood gas analysis:During the experiment,PaO2 in group C maintained stability;PaO2 in group M and group V after the injection of LPS were definitely lower than that in group C(P<0.01);PaO2 in group T decreased, but the downward trend was less than that in group M(p<0.01).PaCO2 in group C show a slightly downward trend in process; after injecting LPS,PaCO2 in group M and V decreased(p< 0.01);PaCO2 in group changes between group C and group M.3. Indexes in serum:Contents of IL-17,IL-22 in serum in group C remained stable during the experiment.Serum IL-17 level in group M and group V significantly increased after the injection of LPS(P<0.05);IL-17 level in group T was between group C and model group.IL-22 contents in group M and group V deseased;IL-22 in group T is higher than that of group C.4. Indexs in Plasma:Before the trial,contents of PAI-1 in plasma had no obvious difference.During the experiment,PAI-1 in group C remained stable.After intravenous injection of LPS,PAI-1 in group M and group V were significantly increased(p<0.05,p<0.01);PAI-1 in group T increased but lower than group M(p<0.05).5. Indexes in bronchoalveolar lavage fluid:Contents of IL-17 in BALF in group M and group V were higher than group C,and the difference was statistically significant(p<0.05);IL-17 contents in group T were between group C and group M.Contents of IL-22 in group T were higher than that in group C,while the contents of IL-22 in group M and group V wre lower than group C without obvious difference between them.6. The wet-to-dry weight ratio of lung tissue:wet-to-dry weight ratio of group M and group V were definitely higher than group C(P<0.01);Group T was definitely lower than model group(p<0.01).7. Indexes of lung tissue:Activities of MPO and contents of IL-17 in lung tissue were significantly higher than that of group C;there was no statistical difference in group T compared with group C.Contents of IL-22 in group T were higher than that of group C;IL-22 in group M and group V were slightly lower than group C,but there was no statistical differences between them.Activities of SOD was significantly lower than group C (p< 0.01);Activities of SOD in group T were between group C and model group.Contents of PAI-1 in group M and group V significantly increased than group C(p<0.05);contents of PAI-1 in group T were lower than model group(p<0.05),but there was no obvious difference when compared with group C(p>0.05).8. Histopathological changes of lung:There was no obvious abnormality in lung tissue of group C. The structures of lung tissue in group M and group V were significantly damaged, such as exudation of protein-rich edema fluid, hemorrhage, inflammatory cells infiltration in alveolar cavities. Alveolar septum widened. Inflammatory cells attached to the wall and microthrombosis could be seen in small blood vessels of pulmonary interstitium. The injury of lung tissue in group T was significantly lighter than that in group M.Conclusion:1. The ARDS model of rabbit can be successfully replicated by intravenous injection of LPS(720μg/kg) at a time.2. Imbalance of the pro-inflammatory and anti-inflammatory reaction, disorder of fibrinolysis and coagulation system, enhanced oxidative stress with relatively insufficient antioxidant capacity, and microcirculation dysfunction are important mechanisms for the occurrence and development of ARDS.3. Curcumin can play a protective role and reduce the injury of ARDS by adjusting inflammation, resisting oxidative stress and balancing the coagulation-fibrinolysis system.