High Salt Induces Proteinuria By Activating P38 MAPK

Objective: Proteinuria is one of the most common clinical manifestation in nephropathy disease,the pathogenesis has not been clarified so far. Over the years, the target drug has been not developed. p38 plays a key role in controlling inflammatory reaction, is one of MAPKs,which could be activated by high salt,ultraviolet radiation.The research on the topic that main from two part which in vitro and vivo to explore the mechanism of the key interacting-factor in producing proteinuria of nephropathy disease. The purpose of the research that study the pathogenesis to develop the targeted therapeutic drugs.Methods: 1.ICR mice(male, 8-10 weeks) were divided into six groups(the number of each group is six.): the normal in high salt group,the single kidney excision in high salt group, the single kidney excision in high salt +p38 inhibitor group, The single kidney excision in the control group,the diabetes mellitus in high salt group,the diabetes mellitus in control group.2.(1)The diabetes mellitus mouse model:Used the 1% STZ to intrapertoneal injection,and measured the blood glucose by cutting-tail method in mice.When the blood glucose >16 mmol/L,and it had held steady,we recruited the mice urine after four weeks.(2)The single kidney excision mice model: left lateral decubitus,and removed the right kidney.After one week,began to recruited the urine.Apart from the single kidney excision in high salt +p38 inhibitor group,gave the 4% saline to the each model mice in high salt group,and the non-salt water to the each model mice in control group. We collected the urine after the mice drinking saline 12 h,24h,36 h,48h, and after stopping the saline 12 h,24h,36 h respectively.3. The single kidney excision in high salt +p38 inhibitor group: when the mice had drank 4% saline 24 h,we singlely injected the p38 inhibitor to the mice by intraperitoneal,collected the urine on the above point-in- time.4.Detected the urine protein by Coomassie Blue Staining and Elisa.removed the spleen to detect the NFAT5 and IL-13 m RNA level in the the single kidney excision in high salt group and the single kidney excision in the control group.5.Divided the new ICR mice(male,8-10 week) into two groups(the number of each group is six):the normal group and the single kidney excision group.6.Separated the mononuclear cell from the spleen and marrow, established the three groups:high salt group.high salt+p38 inhibitor,control group.measured NFAT5 and IL-13 m RNA level.Result: 1. Coomassie Blue Staining and Elisa:the proteinuria in diabetes mellitus model and the single kidney excision group notably exceeded the control group.proteinuria in the two models significantly were superior to the normal group.PCR:IL-13 m RNA level of the single kidney excision model in high salt group above the control group but NFAT5.2.After the cell culture,PCR:NFAT5、IL-13 m RNA level in high salt group significantly exceeded the control group,and NFAT5、IL-13 m RNA level in high salt+p38 inbitor group was inferior to the high salt group.Conclusions: After drinking 4% saline,the proteinuria of the diabetes mellitus model and the single kidney excision model significantly exceed the control group and the normal group. The proteinuria of in the single kidney excision model in high salt + p38 inhibitor group belows the single kidney excision model in high salt group. IL-13 m RNA level in the spleen of the single kidney excision model in high salt group was superior to the control group but NFAT5.When adding the p38 inhibitor,the expression declined.it indicates that when the body was in pathosis,adding the high salt into body,the generation of the proteinuria was related to the expression of NFAT5 and IL-13 after the activation of the p38.