Polydatin Improves Airway Inflammation And Airway Remodeling Through AMPK/Nrf2/HO-1 Pathways In Asthmatic Mice

Objective:1.Whether polydatin can effectively alleviate airway inflammation and reduce the degree of airway remodeling in asthmatic mice models.2.Whether the above effects of polydatin are achieved through AMPK/Nrf2/HO-1 signaling pathways.Methods:Forty 6-week-old BALB/c female mice were randomly divided in to four groups:SAL group,OVA group,OVA+PD30 group,and OVA+PD45 group.Firstly,chronic airway inflammation models were established,including sensitization,administration and challenge.The treatment group was given 0.2 mL of 30 and 45 of polydatin dissolved in normal saline,respectively.The ch allenge was performed for 8 weeks every other day.One hour after the last ch allenge,each group of mice were sacrificed.BALF was collected,the resulting pellet was centrifuged for resuspension and cell smears were prepared for Diff-Quick staining to sort and count inflammatory cells.After centrifugation,the supernatant was taken and tested for IgE,OVA-specific IgE and cytokines IL-4,IL-5,IL-13,IFN-y cytokines by ELISA.The left lung of mice was used to mak e tissue sections for HE,PAS and Masson staining to identify the pathological changes of lung tissue.The expression of AMPK,Nrf2,and HO-1 in lung tissu e was detected by immunohistochemical staining,and the level of a-SMA in lung tissue was detected by immunofluorescence staining.The right lung of mice was used for protein and mRNA extraction.HYP levels in lung homogenates w ere measured by the kit;the expression of a-SMA,AMPK,Nrf2 nuclear,and HO-1 protein levels were measured by Western blot.The expression of Nrf2 nuclear and HO-1 at the mRNA level was detected by real-time PCR.Results:1.Polydatin can effectively alleviate airway inflammation in mice models of asthma,including reducing infiltration of inflammatory cells,goblet cell hyperplasia,mucus secretion,collagen deposition,and regulating the balance of Thl/Th2 cytokines.2.Polydatin can reduce the formation of collagen fibers and inhibit the proliferation of bronchial smooth muscle,thereby inhibiting airway remodeling.3.The the above action of polydatin may be achieved by promoting the activation of AMPK and up-regulating the activation of Nrf2 and enhancing the expression of HO-1 protein.Conclusions:Polydatin can alleviate airway inflammation and airway remodeling in asthmatic mice models,and its mechanism may be related to AMPK/Nrf2/HO-1 signaling pathway.