Experimental Study Of Dexamethasone Therapy For Meconium Aspiration Syndrome In Young Rabbits

Objective:Observe the Clinical Parameter, TNF-a,IL-8and Cyclooxygenase of dexamethasone therapy for young rabbits with meconium aspiration syndromeMethods:Twenty four newborn Japanese big ear rabbits(20-30days old,300-500g) were randomly divided into3groups:(1) control group (n=8):tracheal intubation;(2) saline group (n=8):intravenous injection of equal volume saline at two doses1h and3h after meconium solutions instilled, treated by PAV;(3) dexamethasone group (n=8): intravenous injection of dexamethasone0.5mg/kg at two doses1h and3h after meconium solutions instilled, treated by PAV.saline group and dexamethasone group were gaved two doses of2mL/kg of45mg/ml meconium suspension were introduced deep into the trachea,and three groups were treated by PAV. Parameter adjustment of the ventilator in order to maintain normal range of Tidal volume(6-8ml/kg)、normal Oxygen saturation(85%-95%)-End-tidal carbon dioxide partial pressure(35-45mmHg) and Normal blood gas values.Related parameters recorded were at before(0point) and10minutes after inhaled(0’point), and2,4,6,8h in ventilation, including heart rates, breathing rates, tidal volume, dynamic compliance,Detected arterial blood gas at0’,2h and6h in ventilation, calculated oxygenation index (OI). The animals were sacrificed after8hours continuous ventilation,accounted wet/dry weight ratio, enzyme-linked immunosorbent assay (ELISA) to detect TNF-a, IL-8,COX-1,COX-2in the lung tissue and bronchoalveolar lavage fluid(BALF). Histological lung injury was observed and scored.Results:Animals in each group survived to the end of the experiment1. Physiological indicators:Comparison of saline group and dexamethasone group, there were no statistically significant differences in HR and RR(P>0.05);2.The results of arterial blood gas:At the2h time point and the6h time point, among the three groups, there were no statistically significant differences in PO2,PCO2,and PH(P>0.05).3. Pulmonary Dynamic Compliance: Among the three groups, there was no statistically significant difference pulmonary dynamic compliance at0time point(F=0.073,P=0.789);Other time points there were statistically significant differences;and comparison of the saline group and dexamethasone group the difference were significant.4.Oxygenation Index:Repeated Measure analyzing: The difference was significant in three groups global comparison(F=253.314, P=0.000), Dexamethasone group was significantly higher than the saline group; There were no interactions between time and group(P=1.000);there were statistically significant differences at two time points global comparison(F=27.317, P=0.000),6h was significantly higher than the2h.5. PO2/FiO2:Repeated Measure analyzing: The difference was significant in three groups global comparison(F=3097.358, P=0.000), Dexamethasone group was significantly higher than the saline group; There were no interactions between time and group(P=0.728); there were statistically significant differences at two time points global comparison(F=16.420, P=0.001),6h was significantly lower than the2h.6. Wet/Dry weight ratio:Among the three groups there was statistically significant difference in wet/dry weight ratio (F=48.014,P=0.000), pairwise comparisons were significant differences(P=0.000),and the value of saline group was maximum, the value of control group was minimum.7. Lung injury score:Among the three groups, there was statistically significant difference in the results of lung injury score(F=361.061,P=0.000), pairwise comparisons were significant differences(P=0.000), and the value of saline group was maximum, the value of control group was minimum. 8.The contents of TNF-α、IL-8:In BALF and lung homogenate, the levels of TNF-alpha and Interleukin-8in control group were lower than saline group and dexamethasone group,and dexamethasone group lower than saline group, there were statistically significant differences among the three groups (P<0.05).9.Contents of cyclooxygenase: Among the three groups, there was no statistically significant difference in bronchoalveolar lavage fluid and lung homogenate (P>0.05) levels of cyclooxygenase-1;Compared the levels of cyclooxygenase-2, the differences were significant(P<0.05).Conclusion:1. Meconium aspiration cause excessive release of inflammatory factors, resulting in acute lung injury;2. Dexamethasone inhibits the release of TNF-a, IL-8,COX-2, relieve the induced acute lung injury;3. Dexamethasone can effectively improve the oxygenation status of the lungs of young rabbits with meconium aspiration;4. Dexamethasone could relieved the pulmonary edema and Pathological changes of young rabbits with meconium aspiration;5. Dexamethasone have a more muted effect on the young rabbits with meconium aspiration of the heart rate and respiratory rate.