| Objective:ARDS models of rabbits were replicated with intravascular injection of lipopolysaccharide (LPS) in this study. The possible pathogenic mechanisms such as inflammation and oxidative stress were further studied by observing pathophysiological changes of ARDS models. Furthermore, the effect of glucocorticoid on LPS-induced ARDS in rabbits was investigated, and its possible mechanisms were explored.Methods:Twenty-four New-Zealand white rabbits were randomly assigned to three groups:group A(control group), group B(LPS-treated group) and group C(LPS-treated as group B and treatment with GC group).All rabbits were anaesthetized with 30% ethyl carbamate (4ml/kg) by intraperitoneal injection. The left common carotid artery was separated and intubated for monitoring vital signs and collecting blood samples. ARDS models were reproduced with intravascular LPS(750?g/kg) injection at a time in group B and C. Meanwhile glucocorticoid (4mg/kg) was intravascularly injected as therapeutic method in group C. During the course of the experiment, arterial blood pressure, respiratory rate and arterial blood gas were measured at 0h,0.5h,2h,4h and 6h;contents of TNF-a,IL-10 in serum were detected at 0h,2h,4h and 6h respectively. Contents of TNF-a,IL-10,Trx-1 in lung homogenate, protein expressions of GR,NF-?B p65 and Nrf2 inlung homogenate, the wet-to-dry weigh ratio of lung tissue were also detected after animals sacrificed at 6h.Pulmonary histopathological changes were observed with optical microscope.Results:1. Respiratory rate(RR):During the experiment, RR remained relatively stable in group A. After injecting LPS 0.5h,RRof group B definitely increased, and was significantly higher than that of group A(P=0.000).RR of Group C accelerated, but the tendency was less than group B(P=0.009) and higher than group A(P=0.029).2. Blood pressure(BP):BP of group A showed a trend of slow decrease during the experiment. After injecting LPS 0.5h,BPof group B was significantly lower than that of group A(P=0.000). BPof group C declined, and it was between group A and group B(P=0.000,P=0.005).3. Blood gas analysis:During the experiment,PaO2 and PaO2/FiO2of group Awere maintained stability;PaO2 and PaO2/FiO2 of group B after the injection of LPS were definitely lower than that of group A at 0.5h(P=0.000, P=0.000),which meet ARDS diagnostic criteria;PaO2 and PaO2/FiO2 of group C decreased, but the downward trend was less than that of group B.4. TNF-aand IL-10 level in serum:Contents of TNF-a,IL-10 in serum in group A remained stable during the experiment. Serum TNF-alevel in group B significantly increased after the injection of LPS(P=0.000); TNF-alevel in group C was between group A and group B. Contents of serum IL-10 in group B were higher than those of group A, but there wereno statistical differences until 6h(P=0.046).IL-10 level in group C was significantly higher than those in group A at 2h?4h?6h of experiment(P=0.009, P=0.000,=0.000).5. TNF-a,IL-10 and Trx-1 level in lung tissue:TNF-alevel of lung tissue in group B was significantly higher than that in group A (P=0.000), and TNF-alevel of lung tissue in group C was significantly higher than that in group A (P=0.000) and significantly lower than that in group B (P=0.000). There was no significant difference between group A and B (P=0.109). IL-10 level of lung tissue in group C was significantly higher than that in group A and B(P=0.000, P=0.000). Trx-1 in group B was slightly higher than that in group A, but there was no significant differencebetween both groups(P=0.073). Contents of Trx-1 in group C were significantly higher than thosein group A (P=0.01).6. Expressions of protein for GR, NF-?B p65 and Nrf2 inlung tissue:The expression of protein for GR in lung tissue of group B was lower than that of group A(P=0.002). The expression of protein for GRin group C was significantly higher than that in group B(P=0.01), but slightly lower than that in group A. There was no significant difference between group A and C(P=0.275). The expression of protein for NF-?B p65 in lung tissue of group B was higher than that of group A, and there had statistically significant difference between bothgroups(P=0.000). The expression of protein for NF-?B p65in group C was significantly higher than group A(P=0.002)and lower than group B(P=0.039). The expression of protein for Nrf2in group B and C was significantly higher than that in group A(P=0.002,P=0.001). The expression of Nrf2 in group C was higher than group B, but there was no significant difference between both groups(P=0.334).7. The wet-to-dry weight ratio of lung tissue:wet-to-dry weight ratio of group B was significantly higher than thoseof group A and group C (P=0.000, P=0.000), The ratio of group C was also higher than that of group A (P=0.012).8. Histopathological changes of lung:There was no obviously abnormal structure in lung tissue in group A. The structures of lung tissue in group B were significantly damaged, such as exudation of protein-rich edema fluid, hemorrhage, leukocyte infiltration in alveolar cavities. Alveolar septum was widened and alveolar wall was thicken. Inflammatory cells attached to the wall and microvascular thrombosis could be seen in small blood vessels of pulmonary mesenchyme. The injuries of lung tissue in group C were significantly lighter than those in group B.Conclusion:1. The ARDS model of rabbit can be reproduced by intravenous injection of LPS (750?g/kg) at a time.2. Imbalance of the pro-inflammatory and anti-inflammatory reaction, enhanced oxidative stress with relatively insufficient antioxidant capacity, and microcirculation dysfunction are important mechanisms contributing to the occurrence and development of ARDS.3. Glucocorticoid may play a protective role and reduce the injury of ARDS by antagonizing inflammation, resisting oxidative stress and so on. |
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