Effects of Ambroxol combined with Dexamethasone on acute lung injury induced by lipopolysaccharide in rats

Objective To observe the effects and possible mechanismsof Ambroxol(AMB)/Dexamethasone(DXM)-coadministration on the changes of inflammatory cytokines expression as well as the pathological variations of lung in lipopolysaccharide(LPS)-induced acute respiratory distress syndrome(ARDS). Methods 42 SD rats were divided randomly into 6 groups with 7 each: blank control group(group C), negative control group(group N), positive control group(group L), AMB intervention group(group A), DXM intervention group(group D), AMB and DXM combined intervention group(group AD). Group C was without treatment, group N was given 2 mL of 0.9% NS injection via tail vein; all the other four groups were given LPS of 5 mg/kg; the intervention groups were given AMB(100 mg/kg), DXM(6 mg/kg). All the rats were killed in 6 hours to analysis arterial blood gas and lung tissue wet/dry weight ratio, and then to observe the levels of myeloperxidase(MPO), tumor necrosis factor-α(TNF-α), interleukin-1(IL-1β), as well as the pathological changes in lung. Results Compared with group C, the blood gas analysisimproved significantly [PO2 : group C:(106.4±7.8) mm Hg(1 mm Hg=0.133 kPa), group N:(104.1±7.2) mm Hg, group L:(69.0±4.5) mm Hg, group A:(77.3± 5.4) mm Hg, group D:(78.8 ±6.2) mm Hg, group AD:(86.8±5.6) mm Hg], while the level of W/D ratio [group C:(4.42 ±0.12), group N:(4.39 ±0.13), group L:(5.42 ± 0.05), group A:(4.95±0.16), group D:(4.90±0.12), groupAD:(4.73±0.10)], MPO [group C:(0.35±0.06) U/mg, group N:(0.33±0.04) U/mg, group L:(0.85±0.05) U/mg, group A:(0.55±0.04) U/mg, group D:(0.58±0.05) U/mg, group AD:(0.48±0.04) U/mg], TNF-α [group C:(228.2±18.3) ng/L, group N:(234.6±19.3) ng/L, group L:(719.4±60.2) ng/L, group A:(479.1±29.2) ng/L, group D:(310.9±20.5) ng/L, group AD:(294.7 ±17.5) ng/L], and IL-1β [group C:(0.112 ±0.005) μg/L, group N:(0.116 ±0.002) μg/L, group L:(0.189 ± 0.008) μg/L, group A:(0.144±0.009) μg/L, group D:(0.139±0.013) μg/L, group AD:(0.130±0.007) μg/L] decreased significantly in all the intervention groups. The group C and group N showed normal under optical microscope. Diffused alveolar septum thickening, exudation, edema, ARDS membrane, and the inflammatory granulocyte infiltrating and significant spotty hemorrhage were observed in group L. The histological changes of group A, D, and AD were better than group L. All the results were much more significantly changed in the group which two drugs were combined. Conclusion The combination use of AMB and DXM has cooperative protective effects on acute respiratory distress syndrome induced by LPS in rats. The mechanism may be associated with the common anti-inflammatory effects, the promotion effect of pulmonary surfactant, and also probably related to the common anti-fibrosis and antioxidant effect, leading to the reconstruction of the balance of oxidation and antioxidant system as well as the resluting lung protection.