Research On The Mechanism Of Oxidative Stress Injury Of Systemic Lupus Erythematosus Through The Intervention Of The PRMT1 Regulation System Mediated By Tonifying-kidney And Nourishing-yin Formula

Objective: Discussion on possible mechanisms for intervention in the pathogenetic process of systemic lupus erythematosus(SLE)from a perspective of the PRMT1 regulation system,providing the basis for treatment of SLE with Tonifying-kidney and Nourishing-yin Formula and enriching the theory of TCM prevention and treatment of SLE.Methods: 1.male MRL/lpr mice were randomly divided into 6 groups(n = 6 in each group): model group,low dose group,middle dose group,high dose group,hormone group,traditional Chinese medicine combined with hormone gr oup(combination group).Low dose group,middle dose group and high dose g roup were treated with Formula low medium and high dose model group were given saline gavage,hormone group were given prednisone suspension gavage,traditional Chinese medicine combined with hormone group,middle dose of T onifying-kidney and Nourishing-yin Formula combined with prednisone acetate suspension gavage.After 4 weeks,the rats were killed and the serum was sep arated and the renal tissue was taken out.The contents of SOD,CAT and MD A in serum of each group were detected by ultraviolet spectrophotometry,and the concentration of anti ds DNA antibody was determined by Elisa.The expres sion of PRMT1 and HIF-1a protein in renal tissue of each group were observe d by Western blot,and the levels of SP1,SP3,PRMT1 and HIF-1a were dete cted by quantitative RT-PCR.2.PRMT1 expression level and SP1,SP3,HIF-1a gene expression level and MDA,SOD,CAT content of Pearson correlation a nalysis.Results: 1.compared with the model group,Tonifying-kidney and Nourishing-yin Formula high dose group,hormone group and combination group can decrease MRL/lpr in plasma concentration of anti ds DNA antibody(P<0.01);the treatment groups decreased the content of MDA in serum of MRL/lpr mice(P<0.05,P<0.01),increased serum SOD and CAT content(P< 0.05,P<0.01);Tonifying-kidney and Nourishing-yin Formula high dose group,hormone group and combination group can decrease the expression of PRMT1 and HIF-1a protein levels in renal tissue of MRL/lpr mice;treatment groups were down regulated in kidneys of MRL/lpr mice,PRMT1,SP1,SP3,HIF-1a gene expression level(P<0.01).Compared with the hormone group,combination group(hormone group with Chinese Medicine)can significantly reduce the content of serum MDA(P < 0.01),increased the content of serum SOD,CAT(P < 0.01),down PRMT1,HIF-1a,SP3,PRMT1 and SP1 protein,the expression level of HIF-1a gene(P<0.05,P<0.01).2.the expression level of PRMT1 gene was positively correlated with the expression level of SP1,SP3,HIF-1a and serum MDA(0<r<1,P<0.01),and negatively correlated with serum SOD and CAT(-1<r<0,P<0.01).Conclusion: 1.Tonifying-kidney and Nourishing-yin Formula could reduce the concentration of anti-ds DNA antibody in plasma of MRL/lpr mice,down-regulate expression of PRMT1 of kidney tissue,HIF-1a protein and genes,including PRMT1.SP3,SP3 and HIF-1a,and regulate contents of oxidative stress markers,SOD,CAT and MDA.2.By down-regulation of expression levels of PRMT1,Tonifying-kidney and Nourishing-yin Formula mediated the SP1/SP3--HIF-1a regulation system,down-regulated expression levels of genes,SP1,SP3 and HIF-1a,enhanced contents of serum SOD and CAT and reduced generation of serum MDA to relieve the oxidative stress injury,which might be one of its mechanisms for treatment of SLE.