Esculentoside A (EsA) On The Expression Of ITr35 Cells And IL-35 In MRl/lpr Mice

Objective:By observing the effect of esculentoside A(EsA)on iTr35 and IL-35 in MRL/lpr mice to explore possible mechanism of EsA in the treatment of lupus nephritis.Methods:24 case of female MRL/lpr mice at age of 16 weeks were randomly divided into control group,EsA group and anti-IL-12p35 group.The MRL/lpr mice were treated by RPMI1640 inoculum,EsA and EsA+anti-IL-12p35.Four weeks later,all mice were killed and collect urine,blood and kidney tissue to test rine protein/urine,blood creatinine;Observation of renal pathology by HE,PASM+Masson staining;ELISA was performed to IL-17,IL-35 level;Flow cytometry was performed to evaluate the proportions of(CD4~+Foxp3~-IL-12p35~+IL-27EBI3~+)iTr35 cells.Results:(1)The difference of urine protein/urine creatinine,serum creatinine concentration among the three groups was statistically significant(P<0.05).It was the highest in model control group,followed by EsA+anti-IL-12p35 group,and the lowest in EsA group.(2)Compared with the model control group,the renal pathological manifestations in the EsA group and the EsA+anti-IL-12p35 group were improved to some extent.(3)The difference of IL-35 and IL-17 levels among the three groups were statistically significant(P<0.05),the IL-17 level in the model control group was the highest and the IL-35 level was the lowest,followed by the EsA+anti-IL-12p35 group,while the level of IL-17 in the EsA group was the lowest and the IL-35 level was the highest.(4)Compared with the model control group,the percentage of iTr35 cells in peripheral blood of EsA group and EsA+anti-IL-12p35 group was significantly higher than that of model control group(P<0.05).The percentage of iTr35 cells in peripheral blood decreased after blocking by IL-12p35 antibody,but still higher than that in model control group,the difference was statistically significant(P<0.05).Conclusion:(1)EsA has therapeutic effect on a mouse model of lupus nephritis.(2)The improvement of EsA in MRL/lpr mice may be related to up-regulation of IL-35 expression and induction of iTr35 cell production.(3)EsA may regulate IL-17 through IL-35,thereby exerting pharmacological effects,relieve the condition of lupus nephritis.