Effects of Shenmai Injection regulating SIRT1/PPARγ/NF-κB signaling pathway on immune balance and airway remodeling in obese asthmatic mice

Objective To investigate the effects of Shenmai injection regulating SIRT1/PPARγ/NF-κB signaling pathway on immune balance and airway remodeling in obese asthma mice.Methods C57/BL6J male mice were randomly divided into Control group (Control group), asthma group (OVA group), obesity asthma group (DIO-OVA group), Shenmai injection group (SMI group), SIRT1 activator group (SRT1720 group) and Shenmai injection +SIRT1 inhibitor group (SMI+EX527 group) with 6 in each group Only. The Control and OVA groups were fed standard diet, and the other 4 groups were fed high-fat diet for 12 weeks. After obesity modeling was completed, the other 5 groups of mice were sensitized and stimulated by ovalbumin (OVA) to construct asthma mouse models. Mice in SMI, SRT1720 and SMI+EX527 groups were respectively given drug intervention. Bronchoalveolar lavage fluid (BALF) was taken and leukocyte count was performed. The levels of IFN-γ, IL-4, IL-17A, IL-10, TGF-β1, MMP-9, leptin (Lep) and adiponectin (ADPN) in serum and BALF were determined by ELISA. HE and MASSON staining were used to evaluate the pathological changes of lung tissue. Western blot and RT-qPCR were used to detect SIRT1/PPARγ/NF-κB pathway related proteins and mRNA expression in mouse lung tissues.Result Compared with the Control group, the OVA and DIO-OVA groups had serious pathological injury in lung tissue, the inflammation score of HE staining and the collagen area proportion of MASSON staining were increased (P<0.05), and the total number of white blood cells, the proportion of eosinophils and neutrophils in BALF were increased (P<0.05). The levels of IL-4, IL-17, IL-17/IL-10, TGF-β1, MMP-9 and Lep in BALF and serum were increased (P<0.05), and the levels of P-NF-κB p65 protein and NF-κB p65 mRNA in lung tissue were increased (P<0.05). The levels of IFN-γ, IL-10, IFN-γ/IL-4 and ADPN in BALF and serum were decreased (P<0.05), and the levels of SIRT1, PPARγ protein and mRNA in lung tissue were decreased (P<0.05). Compared with OVA group, the changes of indexes in DIO-OVA group were consistent with the above (P < 0.05). Compared with the DIO-OVA group, the above changes in SMI, SRT1720 and SMI+EX527 groups were reversed (P<0.05). In addition, SMI group mice were treated with SIRT1 inhibitor EX-527, and the therapeutic effect of SMI on obesity asthma was partially blocked.Conclusion Activation of SIRT1/PPARγ/NF-κB pathway can improve immune balance and airway remodeling in obese asthmatics. SMI can improve immune balance and airway remodeling in obese asthmaticmice by activating SIRT1/PPARγ/NF-κB pathway, thus playing a therapeutic role in obese asthma.