| ObjectiveBy using a long-term intervention with low protein diet (LPD), the study is designed toexplore alterations of uric acid, renal function and morphology, urine albumin excretion, hepaticgene expression of key enzymes involving in uric acid synthesis, as well as renal inflammatoryfactors expression in streptozotocin(STZ)-induced diabetic rats.MethodsThirty STZ-induced rats were fed with LPD and normal protein diet (NPD) for12weeksrespectively, twenty control rats were also dispatched into LPD and NPD group. Animal vitalsigns and fasting plasma glucose(FPG), fasting serum insulin(FSI), serum creatinine(sCr), bloodurea nitrogen(BUN), lipid profiles, serum uric acid(SUA) and urinary albumin excretion(UAE),urinary uric acid(UUA), urine creatinine(UCr), urine urea nitrogen(UUN) were measured at thebaseline and3,6,9,12weeks. Rats were killed after12w. Histomorphologic changes of renalwere observed by electron microscope and optics microscope. Expressions of tumor necrosisfactor-α(TNF-α) and vascular endothelial growth factor(VEGF) in renal tissue were detected byimmunohistochemistry. Gene expression of three key enzymes for uric acid synthesis includingphosphoribosylpyrophosphate synthetase1(PRPPS1), phosphoribosylpyrophosphateamidotransferase(PRPPAT) and xanthineoxidase(XOD) was determined by reversetranscription-PCR.Results1. Diabetic rats developed into constant and high level of FPG, SCr, BUN, SUA as well as24h amounts of UCr, UUN, UUA and UAE (P<0.05). LPD in diabetic rats significantlydecreased SUA, BG and UAE (P<0.05) compared with those fed with NPD, left SCr, BUN, UCr, UUN nearly compared between2diet groups (P>0.05). A stepwise linear regression in whichUAE served as independent variable among diabetic rats at9th and12th week (P<0.05) showedthat both FPG and UUA were independent risk factors for DN progression beside FPG.2. LPD slightly inhibit PRPPS1(5.86±3.32vs.6.99±2.14), PRPPAT (9.49±4.41vs.13.36±5.67) and XOD (9.24±7.23vs.12.15±6.06) expression at hepatocytes (P>0.05).3. Glomeruli from diabetic rats were much larger in size than control rats (P<0.05),mesangial cell proliferation and hyaline degeneration of tubular epithelial cell were also severe(P<0.05), while LPD remarkably ameliorated degrees of proliferation and tubular damages(P<0.05).4. Expression of TNF-α in tubular epithelial cell significantly decreased in diabetic rats fedwith LPD (P<0.05), while VEGF expression was comparable between all rats (P>0.05).Conclusions1. STZ-induced diabetic rats show obvious hyperuricemia and renal damages.2. Dysuricemia in STZ-induced diabetic rats mainly characterize by increased uric acidsynthesis in vivo.3. LPD significantly decreases SUA, UAE and ameliorate renal pathologic damages andinflammatory factors expression in DM rats.4. Restored dysuricemia might partly contribute to the attenuation of renal damages inDM rats. |
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