Shenqi Tiaoshen Formula(参芪调肾方)Inhibits COPD Mediated Bone Resorption through OPG/RANKL/NF-κB/MMP-9 Pathway
Objective:To investigate the effects of Shenqi Tiaoshen Formula(参芪调肾方)on inflammation inhibition,lung pathology and osteo-clasts-mediated bone resorption in chronic obstructive pulmonary disease(COPD)model mice established by cigarette smoke(CS)expo-sure.Methods:Forty mice were randomly divided into normal control group,model group,Shenqi Tiaoshen Formula 8.53 g/kg,17.06 g/kg and 34.11 g/kg groups,with 8 mice in each group.Except for the normal control group,the mice in the other four groups were exposed to CS for 24 weeks,and the mice in each group were given corresponding drugs or normal saline by intragastric administration from the 12th to the 24th week continuously.The contents of inflammatory factors interleukin-1(IL-1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in lung tissue,peripheral blood and bone tissue were detected by ELISA.HE staining was used to observe the pathological changes in lung tissue.Tartrate-resistant acid phosphatase(TRAP)staining was used to observe osteoclast in bone tissue.Immunohistochemical method was used to detect the localization and expression of osteoprotegerin(OPG),receptor activator of nuclear factor κB ligand(RANKL),nuclear fac-tor κB p65(NF-κB p65)and matrix metalloproteinase-9(MMP-9)in tibia tissue of mice.The protein expression of NF-κB p65,p-NF-κB p65,MMP-9 in lung tissue and OPG,RANKL,NF-κB p65,p-NF-κB p65,MMP-9,cathepsin K(CTSK)in tibia were detected by Western blot.Results:Compared with the normal control group,the lung tissue of the model group was significantly damaged,and a large number of inflammatory cells were gathered in and around the lumen and tube wall.The contents of inflammatory factors IL-1β,IL-6 and TNF-α in lung tissue,peripheral blood and bone tissue were significantly increased(P＜0.01).The number of osteoclasts and the protein expressions of RANKL,NF-κB p65,MMP-9,CTSK and TRAP in bone tissue were significantly increased(P＜0.01),while the protein expression of OPG was significantly down regulated(P＜0.01).Compared with the model group,each dose group of Shenqi Tiaoshen Formula could improve the bronchial wall thickening,emphysema formation and other pathological changes in mice to different degrees,and reduce inflammatory cell infil-tration.Shenqi Tiaoshen Formula 34.11 g/kg group could significantly reduce the protein expressions of NF-κB p65,P-NF-κB p65 and MMP-9(P＜0.01),and reduce the contents of inflammatory factors IL-1 β,IL-6 and TNF-α(P＜0.01).The number of osteoclasts and pro-tein expressions of RANKL,NF-κB p65,p-NF-κB p65,MMP-9,CTSK and TRAP in the bone tissue of Shenqi Tiaoshen Formula 34.11 g/kg group were significantly down regulated(P＜0.05 or P＜0.01).OPG protein was significantly increased(P＜0.01).Conclusion:Shenqi Tiaoshen Formula has certain preventive and therapeutic effects on COPD model mice complicated with osteoporosis(OP),which may be me-diated by regulating OPG/RANKL/NF-κB/MMP-9 signaling pathway,improving lung pathology,reducing inflammation in lung,peripheral blood and bone tissue and inhibiting osteoclast overactivation in COPD model mice.
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