Expression And Significance Of P53/SAT1/ALOX15 Ferroptosis Pathway In Skeletal Muscle Tissues Of Animal Model Of Idiopathic Inflammatory Myopathy

Objective: The aim of this study was to establish EAM mice model by immunizing BALB/c mice with guinea pig skeletal muscle homogenate,and to detect the iron staining and the protein expression levels of p53,SAT1 and ALOX15 in muscle tissues of EAM mice and control mice by prussian blue staining and immunohistochemistry,so as to study and explore the significance of p53/SAT1/ALOX15 ferroptosis pathway in the pathogenesis of idiopathic inflammatory myopathy,and provide new directions for its diagnosis and treatment.Methods: EAM mouse model was established by subcutaneous injection of roughly extracted guinea pig skeletal muscle homogenate mixed with complete Freund’s adjuvant.The clinical performance score,muscle strength status,body weight,serum CK level and pathological grade of HE staining of mice in the EAM group and the control group were compared to determine whether the EAM mouse model was established successfully.Immunohistochemistry and prussian blue staining were used to detect the protein expression levels of p53,SAT1,and ALOX15 and iron staining in skeletal muscle tissues of EAM mice and control mice,respectively.Results: The expression levels of p53,SAT1 and ALOX15 in EAM group were higher than those in the control group(P<0.05);The blue particles(iron deposition)in skeletal muscle tissues of mice in EAM group were significantly higher than those in the control group.The immunohistochemical score of p53 was positively correlated with the immunohistochemical score of SAT1 and ALOX15(P <0.05),and the immunohistochemical score of SAT1 was positively correlated with the immunohistochemical score of ALOX15(P<0.05).The HE staining score of muscle tissue of EAM mice was positively correlated with the immunohistochemical score of p53,SAT1 and ALOX15,respectively(P<0.05).Conclusion: P53 may be involved in the pathogenesis of IIM by promoting the up-regulation of SAT1 expression and further inducing the expression of ALOX15.The overexpression of p53,SAT1,and ALOX15 and the accumulation of iron ions may lead to ferroptosis,and the more expression of p53,SAT1,and ALOX15,the more severe the muscle inflammatory lesions and the more severe the muscle damage.