Study On The Effect And Mechanism Of Baicalin Against Hyperuricemia Nephropathy

With the improvement of living standards,the incidence of hyperuricemia and nephropathy is increasing At present,the treatment of hyperuricemia nephropathy mainly uses allopurinol,a drug that inhibits uric acid production,benzbromarone that promotes uric acid excretion,and dexamethasone,which is an anti-inflammatory drug.Although these drugs have certain effects,they have large side effectsl,low clinical compliance,no renal protection and are not suitable for long-term treatment..Baicalin is a flavonoid compound with good antioxidant and anti-inflammatory effects,and has the potential to be developed as a drug against hyperuricemia nephropathy.Therefore,Firstly,this article studied the inhibitory effect of baicalin on XOD in vitro,.Then,the protective effect of baicalin on hyperuricemia and nephropathy and its mechanism were studied in animal models.Lastly,a model of sodium urate crystal(MSU)induced inflammation of renal tubular epithelial NRK-52 e cells was established,and the effect of baicalin on the injury of renal tubular epithelial cells induced by sodium urate crystals was studied.(1)The in vitro ultraviolet absorption kinetics method was used to investigate the inhibitory effect of baicalin on XOD,and the molecular docking technique was used to study the possible mechanism of the inhibitory effect of baicalin on XOD.The results show that baicalin can inhibit the activity of XOD to a certain extent,and it is a mixed inhibitory effect on XOD;molecular docking shows that baicalin can bind to the active center of XOD,preventing the substrate hypoxanthine or xanthine from entering the active center Inhibit XOD activity(2)A model of hyperuricemia nephropathy in mice was prepared by using yeast extract combined with potassium oxazidate,and the effect of baicalin on hyperuricemia nephropathy was explored.Compared with the model group,each dose group of baicalin can significantly reduce the serum uric acid level(P <0.05 or P<0.01),urea nitrogen and creatinine levels(P <0.05,P <0.01)in mice;it can significantly reduce the mice Liver XOD activity(P <0.01);medium and high doses of baicalin can significantly reduce the liver coefficient of mice(P <0.05,P <0.01);each dose of baicalin can significantly reduce the kidney and spleen coefficients of mice(P <0.05,P <0.01);each dose group of baicalin can significantly reduce the area of white spots on the kidney surface;each dose group of baicalin can reduce inflammation in renal cortical area,renal tubular disorder,glomerular enlargement,renal tubular Cavity protein-like content,renal cell necrosis,and renal fibrosis(3)Using NRK-52 e cells as the research object,the cell morphology,the content of lactate dehydrogenase,NO,TNF-α and IL-1β in the supernatant were used as the evaluation indicators to establish the MSU-induced renal tubular epithelial cell injury model and explored the Scutellaria baicalensis Effects of glycosides on renal tubular epithelial cell injury induced by sodium urate crystals.Compared with the model group,the baicalin high-dose group can significantly inhibit the release of lactate dehydrogenase(P <0.05);the group can significantly reduce the secretion of NO(P <0.05,P <0.01);it can significantly inhibit TNF-α,The content of IL-1β(P<0.05 or P <0.01);each dose group of baicalin showed a dose-dependent inhibition of renal tubular epithelial cell apoptosis and ROS levels in cells.In summary,baicalin can inhibit the activity of XOD,inhibit the production of uric acid,reduce the serum uric acid level in mice with hyperuricemia nephropathy,and can significantly improve the kidney function of mice,and reduce the damage of appearance and pathology of mouse kidney.Baicalin reduces the secretion of lactate dehydrogenase,NO,TNF-α,IL-1β,inhibits apoptosis and reduces the level of cellular ROS,thereby inhibiting the damage of sodium urate crystals to renal tubular epithelial cells in rats.