| Aims: Hyperuricemia is a metabolic disease in which abnormal uric acid metabolism causes blood uric acid levels in the body to exceed the normal physiological concentration.A chronic physiological state of high urate in the body can lead to deposition of urate crystals in the joints and kidneys,leading to gout and gouty nephropathy.The purpose of this study was to study the effect of Fufang Zhenzhu Tiao Zhi(FTZ)on hyperuricemia and gouty nephropathy induced by hypoxanthine(Hx)combined with potassium oxonate(OXO)and to explore its mechanism.Method: 1.Male Balb/c mice were divided into normal group,HX-100+OXO-500,HX-200+OXO-500,and HX-300+OXO-500 in the experimental model of hyperuricemia and gouty nephropathy.The model group was continuously administrated intragastrically for 21 days,while the normal group was administrated CMC-Na as control.On the 21 st day,mouse samples were collected.Blood uric acid and XOD activities were detected to evaluate hyperuricemia,kidney injury was observed by HE,Masson and Gomori staining,and the RNA levels of URAT1,GLUT9,OAT1,ABCG2,KIM1 and FN in kidney were detected by Quantitative Real-time PCR(q-PCR).2.In the experiment of improving hyperuricemia and gouty nephropathy induced by Hx combined with OXO by FTZ.Male Balb /c mice were divided into Normal group,HUA group,AP group,BM group,FTZ low dose(FTZL)group,FTZ high dose(FTZH)group.The positive drug and the test drug FTZ were administered by gavage of Hx combined with OXO.After 21 days,the urine of mice for 24 hours was collected by metabolic cage,and tissue specimens of mice were collected.Biochemical indexes(SUA,SCr,BUN,XOD,ALT)were detected,and kidney tissues of mice were taken for pathological sections,and renal injury was observed by pathological staining(H&E,Sirius red,Masson,Gomori,PAS staining).Kidney(NLRP3,IL-1β,IL-18,MCP-1,URAT1,GLUT9,OAT1,ABCG2,KIM1,FN)were detected by q-PCR.3.UA-induced renal injury and fibrosis of human tubular epithelial(HK-2)cells were treated with different doses of FTZ to verify the protective effect of FTZ on kidneys and its mechanism of action.Results: 1.Intragastrical administration of Hx combined with OXO can significantly induce the increase of serum uric acid in mice.H&E,Masson and Gomori staining results showed that hyperuricemia induced by Hx combined with OXO further involved the kidneys and caused gouty nephropathy.The mice hyperuricemia and gouty nephropathy model induced by Hx-300+OXO-500 dose group were more successful and stable.2.In mice with hyperuricemia and gouty nephropathy induced by Hx combined with OXO,FTZ was given at the same time.Compared with the model group,the level of serum uric acid in the FTZ group was significantly down-regulated and the deposit of renal urate was reduced.H&E,PAS,Sirius red and Masson staining were observed under microscope.The deposition of collagen and inflammation were reduced in the kidney of mice in the FTZ group.3.In vitro assay,compared with the control group,the collagen deposition of HK-2 cells was significantly increased after UA stimulation,and the renal tubular epithelial cells were seriously damaged.Compared with the UA group,the FTZ group inhibited inflammatory cytokines and improved collagen deposition.Conclusion: Hyperuricemia is caused by elevated levels of uric acid that often accumulate in the kidneys,resulting in gouty nephropathy,with more severe tubular damage.After FTZ treatment,it can improve inflammation,reduce the kidney fibrosis caused by collagen deposition,and play a protective role in the kidney... |
PDF Full Text Request