Study On The Improvement And Mechanism Of Action Of Sophora Flavescens And SRI On RA Model Mice Based On "ferroptosis

Purpose: The mechanism of Sophoridine(SRI)and Sophoridine decoction on rheumatoid arthritis(RA)model mice was studied.Factors related to "iron death" were detected: GSH,GPX4 and SLC7A11 to prove the correlation between RA and "iron death".To clarify the mechanism of sophora flavescens decoction and SRI on RA,and to explore a new idea and method for the treatment of RA by traditional Chinese medicine.Materials and Methods:RA model mice were induced by bovine collagen type Ⅱ protein.The successful modeling was determined by the evaluation of Arthritis Index(AI),joint diameter,swelling degree,activity level,body weight,observation of local skin color changes and hematoxylin-eosin(HE)staining of each mouse.Mice were given matrine decoction,SRI low dose and SRI high dose intragastrically.The blank control group and RA model group were compared,and the effects of each medication group on RA were analyzed,including AI evaluation,joint diameter,swelling degree change,activity level,body weight and local skin color change of each mouse.HE staining was used to score the cell proliferation,inflammatory cell erosion and bone erosion in the synovial tissue of knee,ankle and toe of blank control group,RA model group and matrine group.The "iron death" related factors were detected.The contents of ROS and GSH in serum of the five groups of mice were detected by enzyme-linked immunosorbent assay(Elisa).The expression levels of SLC7A11 and GPX4 in knee,ankle and toe of the five groups of mice were detected by immunohistochemical assay(IHC).Ferric ion content in five groups was detected by Prussian blue staining,and the content of ferric ion in each group was compared.The content of interleukin 18(IL-18)was determined by Elisa.Results:1.Through AI evaluation of experimental mice,ankle joint diameter measurement,swelling degree change,activity,weight and local skin color change,and HE staining method,RA model mice can be successfully constructed.2.Matrine decoction and SRI can improve RA model mice,and Matrine and SRI high-dose group can improve significantly compared with SRI low-dose group.3.The results of HE staining showed that sophora sophora could improve the proliferation of synovial cells,inflammatory cell erosion and bone erosion in knee,ankle and toe joints of RA model mice to some extent.4.Elisa results showed that ROS and IL-18 concentrations in RA group were higher than those in blank control group.The concentrations of ROS and IL-18 in medication group were lower than those in RA group.The concentration of sophora flavescens group and SRI high-dose group was lower than that of SRI low-dose group.5.Elisa results showed that the concentration of GSH in RA group was lower than that in blank control group;The concentration of GSH in medication group was higher than that in RA group.The concentration of sophora flavescens group and SRI high-dose group was higher than that of SRI low-dose group.6.Immunohistochemistry(IHC)results showed that the gray values of GPX4 and SLC7A11 in RA group were higher than those in blank control group,and the gray values of GPX4 and SLC7A11 in medication group were lower than those in RA group.The gray values of sophora flavescens group and SRI high-dose group were lower than those of SRI low-dose group.The gray value of SLC7A11 was higher in the ankle joint after modeling,which is worthy of further discussion.7.Prussian blue staining results showed that more Fe3+ was dyed blue in RA group than in blank control group;The blue part of medication group was less than that of RA group.Among them,the blue part of matrine treatment group and SRI high-dose group was less than that of SRI low-dose group.Conclusion:1.Matrine decoction can improve cell proliferation,inflammatory cell erosion and bone destruction in synovial tissue of knee,ankle and toe joints of RA model mice.2.Sophora flavescens decoction and SRI can activate the expression of GSH,GPX4 and SLC7A11 to a certain extent.3.Sophora flavescens decoction and SRI can inhibit the expression of ROS and IL-18 to a certain extent.4.Sophora flavescens herbal decoction and SRI may ameliorate RA symptoms by regulating "iron death".