基于SDF-1/CXCR4信号通路探究紫檀芪对特应性皮炎小鼠的治疗作用及机制OA

Objective To explore the healing effect and mechanism of pterostilbene(PTE)on atopic dermatitis(AD)mice based on stromal cell-derived factor-1(SDF-1)/chemokine receptor type 4(CXCR4)signaling pathway.Methods A BALB/c mouse model of AD was established by applying 2,4-dinitrochlorobenzene(DNCB)to the back of the mice.The successfully modeled mice were assigned into Model group,L-PTE group,M-PTE group,H-PTE group(gavage of 20,40,and 80 mg/kg PTE),and NUCC-390 group(gavage of 80 mg/kg PTE+intraperitoneal injection of 3.2 mg/kg SDF-1/CXCR4 signaling pathway activator NUCC-390),each with 10 mice.Another 10 normal mice were designated as the control group,and both the control group and the Model group were given an equal amount of physiological saline,once a day for 28 consecutive days of intervention.The skin lesions of mice in each group were observed and scored.The skin thickness of the affected area was measured.The 10 minute scratching frequency of mice in each group was recorded.HE,toluidine blue,and Masson staining were used to observe the pathology of mouse skin lesions,the number of mast cells,and the generation and arrangement of collagen,respectively.ELISA was used to detect TNF-α,IL-4,IL-6,interferon-γ(IFN-γ),and immunoglobulin(IgE)in mouse serum.Western blot was used to detect SDF-1/CXCR4 signaling pathway related proteins in mouse skin lesions.Results For the control group,the back skin of mice in the Model group showed edema,erythema,scales,decreased collagen fibers,disordered arrangement,raised skin lesion thickness,increased number of scratches and infiltration of mast cells,and increased TNF-α,IL-4,IL-6,IgE,SDF-1,and CXCR4(P＜0.05),while IFN-γ level was significantly decreased(P＜0.05).For the Model group,the L-PTE group,M-PTE group,and H-PTE group showed reduced swelling,erythema,and scales on the back skin,increased collagen fibers arranged neatly,clearly reduced skin lesion thickness,clearly reduced scratching frequency and number of mast cell infiltration,and clearly decreased TNF-α,IL-4,IL-6,IgE,SDF-1,and CXCR4(P＜0.05),while IFN-γ was significantly increased(P＜0.05).For the H-PTE group,the NUCC-390 group showed increased swelling,erythema,and scales in the back skin of mice,decreased collagen fibers,disordered arrangement,clearly raised skin lesion thickness,clearly raised scratching frequency,and increased infiltration of mast cells,and clearly increased TNF-α,IL-4,IL-6,IgE,SDF-1,and CXCR4(P＜0.05),while IFN-γ was significantly decreased(P＜0.05).Conclusion PTE has a promoting effect on the treatment of AD mice by inhibiting SDF-1/CXCR4 signaling pathway and suppressing inflammatory responses.