Effect And Mechanism Of High Flow Nasal Oxygen Therapy Combined With Ambroxol On Pulmonary Inflammation Injury In ARDS Rats

Objective To investigate the therapeutic effect of HFNC oxygen therapy combined with AMB intervention in ARDS,we established rats model of LPS treated with two strikes.Then we explore the mechanism of the joint intervention of NF-κB signal pathway and Nrf2-HO-1/NQO1 anti-oxidative stress signal in ARDS,and provide new ideas and methods for clinical treatment of ARDS,in order to optimize ICU nursing work.Methods To investigate the therapeutic effect of HFNC oxygen therapy combined with AMB intervention in ARDS,we established rats model of LPS treated with two strikes,SD rats were randomly divided into normal control group,ARDS control group,HFNC oxygen therapy group,AMB treatment group and combined（HFNC+AMB）treatment group,with 8 rats in each group.The HFNC oxygen therapy group was given humidified and heated through the nasal tube with a high flow rate of oxygen.The AMB treatment group was given AMB by the method of injecting into the tail vein once a day.The Combined（HFNC+AMB）treatment group was given humidification and high-flow oxygen supply to the material and tail vein injection of AMB once a day.In normal control group and ARDS control group,the tail vein administration were replaced with PBS.Blood and lung tissue were taken on the 5th day of treatment.We observed analysis of arterial blood gas,ratio of lung wet/dry weight,and lung tissue pathological changes of five groups.The MPO activity of lung tissue was detected by colorimetry.The expressions of IL-1,IL-6,TNF-α,NF-κB,Nrf2,HO-1 and NQO1 mRNA of lung tissue were detected by q PCR.The tissue immunofluorescence staining and Western blot were used to detect the expression of NF-κB in lung tissue.Results 1.The arterial partial pressure of oxygen（PaO₂） and oxygen saturation（SaO₂） in ARDS control group were significantly lower than those in the normal control group（P<0.01）.The PaO₂ and SaO₂ increased to different extents in HFNC oxygen therapy group,AMB treatment group,combined（HFNC+AMB）treatment group,and the differences were statistically significant（P<0.05）,and also PaO₂ and SaO₂ of combined（HFNC+AMB）treatment group were higher than HFNC oxygen therapy group and AMB treatment group.2.Compared with normal control group,the W/D ratio of lung tissue in ARDS control group decreased significantly（P<0.01）.Compared with ARDS control group,the W/D ratio of HFNC oxygen therapy group and AMB treatment group decreased（P<0.05）,and（HFNC+AMB） treatment group showed a significant downward trend（P<0.01）.3.HE staining of lung tissue showed extensive tissue consolidation and bronchiole inflammation,airway epithelial necrosis,inflammatory cell infiltration,diffuse alveolar damage with edema and hemorrhage in the lung tissue of ARDS control group.In HFNC oxygen therapy group,there were inflammatory cell infiltration around bronchioles and alveoli,and the alveolar wall was thickened with inflammatory exudation.In AMB treatment group,there were mild bronchiolitis,a small amount of alveolar damage with hemorrhage and inflammatory cell infiltration.The combined（HFNC + AMB）treatment group had mild bronchioles and alveolar inflammation.4.The results of colorimetric assay showed that the MPO activity in the lung tissue of the ARDS control group was significantly higher than that of the normal control group（P<0.01）.Compared with ARDS control group,the MPO activity decreased significantly in HFNC oxygen therapy group,AMB treatment group,and combined（HFNC+AMB） treatment group（P<0.01）,and combined（HFNC+AMB） treatment group decreased more than the HFNC oxygen therapy group and AMB treatment group.5.The q PCR results showed that the levels of IL-1,IL-6,TNF-α,NF-κB,Nrf2,HO-1 and NQO1 in ARDS control group were significantly higher than those in the normal control group（P<0.01）.Compared with ARDS control group,the expressions of IL-1,IL-6,TNF-α,and NF-κB mRNA were significantly decreased in HFNC oxygen therapy group,AMB treatment group,and combined（HFNC+AMB） treatment group（P<0.01）,while the levels of Nrf2,HO-1 and NQO1 mRNA in the oxygen therapy group,AMB treatment group and combined（HFNC+AMB） treatment group increased to different degrees（P<0.05）.And the proportion of decline/rise in the combined（HFNC+AMB） treatment group were higher than HFNC oxygen therapy group and AMB treatment group.6.The results of NF-κB by immunofluorescence intensity analysis and Western blotting showed that the expression of NF-κB in ARDS group was significantly higher than that in normal control group（P<0.01）.Compared with ARDS control group,the expression of NF-κB was significantly lower in HFNC oxygen therapy group,AMB treatment group,and combined（HFNC+AMB） treatment group（P<0.01）,and also the combined（HFNC+AMB） treatment group was lower than the HFNC oxygen therapy group and AMB treatment group.Conclusions The combination of HFNC and AMB inhibited the expression of inflammatory cytokines by down-regulating the NF-κB signaling pathway,and promoted the oxidation-antioxidant balance by up-regulating the anti-oxidative stress signal of Nrf2-HO-1/NQO1,then effectively alleviated LPS-induced acute lung Injury and played a role in the treatment of ARDS.