五味子乙素调节Noxa/Hsp27/NF-κB信号通路对哮喘大鼠气道炎症和气道重塑的影响OA北大核心CSTPCD

Objective:To investigate the impacts of Schisandrin B(Sch B)on airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Heat shock protein 27(Hsp27)/nuclear factor-κB(NF-κB)signaling pathway.Methods:SD male rats were randomly separated into control group(normal feeding),asthma group,Sch B-L group(40 mg/kg),Sch B-H group(80 mg/kg),positive control group(0.5 mg/kg dexamethasone),Vector group(tail vein injection of empty plasmid+80 mg/kg Sch B),Noxa group(tail vein injection of Noxa overexpression plasmid+80 mg/kg Sch B),with 6 rats in each group.Except the control group,6 groups of rats were sensitized and stimulated with ovalbumin to establish asthma rat model,and were given drug intervention,once a day for four weeks.RT-qPCR was applied to measure the expression of Noxa in lung tissue;differential white blood cell counts in bronchoalveolar lavage fluid(BALF)were performed;ELISA was applied to measure the levels of IL-4,INF-α,IL-13 and IL-5 in rat serum;HE staining was applied to observe the histopathology of lung tissue of rats in each group;expression of Noxa protein and phosphorylation levels of Hsp27 and NF-κB in lung tissue were detected by Western blot.Results:Compared with the Vector group,the expression lev-el of Noxa in the left lung tissue of the Noxa group was obviously increased;compared with the control group,the right lung tissue structure of the rats in the asthma group was obviously damaged,the tracheal tube was obviously narrowed,the interstitium was mas-sively inflammatory infiltration,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the cir-cumference of the basement membrane were obviously increased,and the cells in the BALF were obviously increased,the total num-ber,eosinophils,neutrophils,and lymphocytes were obviously increased,and macrophages were obviously decreased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously increased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tissue were obviously increased(P<0.05);compared with the asthma group,the duct stenosis in the right lung tis-sue of the Sch B-L group,the Sch B-H group and the positive control group were obviously improved,the inflammatory infiltration was reduced,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the circumference of the base-ment membrane were obviously reduced,and the cells in the BALF were obviously reduced,the total number,eosinophils,neutro-phils,and lymphocytes were obviously decreased,and macrophages were obviously increased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously decreased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tissue were obviously decreased and was dependent on dose(P<0.05);overexpression of Noxa attenuated the ameliorating effects of Sch B on airway inflammation and airway remodeling in asthmatic rats.Conclusion:Sch B can effectively ameliorate airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Hsp27/NF-κB signaling pathway.