Protective Effect Of Iridiod Glycosides From Paederia Scandens On Uric Acid Nephropathy Rats And Its Mechanisms

Uric acid nephropathy (UAN) also known as gouty nephropathy is due to excessive concentrations of uric acid urate deposition in the kidney, kidney damage caused by the crystallization. Iridiod Glycosides from Paederia Scandens (LOUR.) MERRILL (Rubiaceae) ( IGPS) are asperuloside,paederoside,scandoside et al. Our former studies showed that extracts paederia scandens have clear protective effects on experimental hyperuricemia and gouty arthritis. This study is intended to further investigate the effect of IGPS on uric acid nephropathy in rats and its possible mechanism. The main experimental results are as follow:1 Protective effect of iridiod glycosides from paederia scandens on uric acid nephropathy in ratsThe experimental animal model of the uric acid nephropathy was induced by i.g. of adenine(100mg/kg, ig, qd×28d)and i.p.of potassium oxonate (250mg/kg, ip, qw). Every day during the experiment to observe the demeanor of fur color in rats, fed into the water, urine and behaviors and so on. From the fouth day, every AM model by administering and every PM do through oral administration (280, 140, 70 mg/kg) for groups of IGPS, the AP group and the BEN group, until the end of modeling. With ig of 0 days, 7d, 14d and 24d to monitor changes in body weight in rats. Detection of the rats after 28 days of uric acid (UA), urea nitrogen (BUN), creatinine (Cr), renal index.Conventional HE staining, optical microscopy of renal pathological changes.The results show that IGPS (280,140,70 mg/kg, ig, qd×24d) could improve the uric acid nephropathy general symptoms, and could promote the growth of body weight differently in UAN rats, lower serum uric acid, improve renal function, lower kidney index. Renal pathology by light microscopy showed IGPS(280,140,70 mg/kg, ig, qd×24d) could reduce the renal tissue urate deposition, reduce the renal inflammatory cell infiltration and tissue fibrosis.These findings indicate that IGPS has better preventive and therapeutic effect on uric acid nephropathy in rats induced by adenine and potassium oxonate.2 Protective effects of iridiod glycosides from paederia scandens on uric acid nephropathy rats and its mechanisms2.1 Effect of IGPS of xanthine oxidase activity on UAN rats Enzyme assay was used to detect serum and liver xanthine oxidase (XO) activity.The results showed that IGPS (280, 140, 70 mg/kg, ig, qd×24d) could significantly inhibite uric acid nephropathy in rats serum and liver of XO activity. These results suggest that the uric acid nephropathy effect is partly due to inhibite serum and liver of XO activity.2.2 Effect of IGPS on uric acid metabolism in UAN ratsPhosphotungstic acid method was used to determine urine uric acid, urine creatinine, and urine volume levels in UAN rats, and uric acid excretion in rats was calculated. The results showed that IGPS (280,140 mg/kg, ig, qd×24d) could significantly increase the uric acid nephropathy in rats'urine uric acid levels ,IGPS (280,140 mg/kg, ig, qd×24d) could enhancement urate clearance of uric acid in UAN rats and IGPS (280,140, 70 mg/kg, ig, qd×24d) on the uric acid nephropathy in rats urine creatinine and urine volume had no significant effect.These results suggest that the uric acid nephropathy effect is partly due to increase uric acid clearance in UAN rats.2.3 Effect of IGPS on inflammatory cytokines in UAN ratsThe NF-κBp65 and MCP-1 protein expression were investgated by immunohistochemistry, MCP-1mRNA levels were monitored by RT-PCR. The results showed that IGPS (280, 140, 70mg/kg, ig, qd×24d) could significantly reduce the NF-κBp65 and MCP-1 protein expression in UAN rats kidney tissue, inhibit NF-κB to the nucleus transfer and reduce the expression of MCP-1mRNA. This evidences showed IGPS could effectively protect the inflammatory cytokines mediated tubulointerstitial injury, which may be an important mechanisms of its renal protection in UNA rats.2.4 Effect of IGPS on fibrosis in UAN rats kidney tissueTheα-SMA protein expression was investgated by immunohistochemistry and theα-SMAmRNA levels were monitored by RT-PCR. The results showed that IGPS (280, 140mg/kg, ig, qd×24d) could down-regulateα-SMA protein expression andα-SMAmRNA expressions. These results showed IGPS could effectively improve renal fibrosis on UAN ratsConclusion: IGPS has good preventive and therapeutic effect on uric acid nephropathy rat model induced by adenine and potassium oxonate, and its mechanisms might be related to decrease serum uric acid, inhibit xanthine oxidase activity, to accelerate uric acid clearance, improve kidney inflammation andrestrain the degree of renal fibrosis.