| Objective:The protective effect of EPS on GN was investigated and its mechanisms w ere preliminary studied.Methods:1.GN model was established by combination of adenine and potassium oxon ate.EPS of different origins was continuously administered for two weeks.Bioch emical indicators,kidney changes,expression of related uric acid transporters we re analyzed to study their resistance.2.HK-2 cellswere stimulatedwith UA and its vitality was evaluated by MTT,the expression of uric acid transporter,phenotype-transformed protein,and renal i njury molecules are measured by Western-Blot to study the protective effect of E PS on HK-2 cells.3.The levels of IL-1β in renal tissue of GN ratswere measured by ELISA,t he inflammatory environment of HK-2 cells was stimulated by IL-1β,the express ionof ABCG2 was detected by Western-Blot to studythe mechanisms of EPS on kidney protection.Use network pharmacology analysis methods to make C-T chart s and T-P charts to further explore possible mechanisms.Results:1.The results of biochemical indicators showed that EPS can reduce the lev els of UA,CRE and BUN in serum of rats with GN;HE staining results sugge sted that EPS groups had curative effect on GN,and the degree of renal damag e in sample group 5 was the smallest;Western-Blot results showed that the EPS of each group could up-regulate the ABCG2 level in the rat kidney,and the sa mple1,2,5 could reduce the level of the URAT,and the 5th sample could reduc e the level of the GLUT9.2.MTT assay showed that EPS has protective effect on uric acid-induced inj ury of HK-2 cells.Cell viability increased when the EPS increased.Western-Blot results showed that EPS up-regulated the expression of ABCG2 and OAT1 in HK-2 cells and down-regulated the expression of URAT1 and GLUT9;EPS incre ased the E-cadherin level and reduced α-SMA level;EPS decreased KIM-1 expre ssion.3.ELISA results showed that EPS could reduce IL-1β levels in serum of rat s with GN,Western-Blot results showed that with increasing IL-1β content,ABC G2 level increased,adding PDTC can reduce ABCG2 protein expression level.Ne twork pharmacological analysis revealed that EPS may protect the kidney byfour major targets and six major pathways and NF-κB was the target which has the most related pathways.Conclusion:EPS has a protective effect on renal damage induced by hyperuricemia in ra ts.No.5 sample has the best effect.EPS has a protective effect on renal tubular epithelial cells damage induced by uric acid in vitro and affects the expression of Uric Acid Transporter,Phenotypic Transforming Protein,RenalInjury Molecule s.EPS may affect the excretion of uric acid by decreasing the expression of AB CG2 by decreasing IL-1β and mediating the activation of NF-κB. |
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