Study Of The Endothelial Dysfunction In Hyperuricemia Nephropathy Rats And The Effect Of Intervention

Objective1.To establish the rat model of chronic primary hyperuricemia renal damage;2. To discuss the role of vascular endothelial dysfunction in the pathogenesis of hyperuricemia nephropaihy;3. To discuss the renal protection significance by the early intervention of hyperuricemia.Methods45male wister rats were randomly divided into three groups, namely control group, hyperuricemia model group,benzbromarone treatment group, n=15. Application of Oteracil potassium(uricase inhibitor) and high yeast feed to establish the hyperuricemia model, In addition to giving the same treatment,the the treatment group were added benzbromarone to control hypeuricemia. Control group were fed normal diet and tap water, at the weekend of2,4,6, blood uric acid and creatinine level were tested, all rats were sacrificed at the end of6week ans, the renal tissue was taken to observe the the naked eye change. HE and Masson staining of renal organizations to observe the pathological changes and measure the interstitial fibrosis area. The endothelial of nitric oxide synthase (Endothelium nitric oxide synthase, eNOS)、endothelin-1(Endothelin1, ET-1) hypoxia inducible factor-1α(Hypoxia-induced factor-1α, HIF-1 α) expression in renal interstitial tubular was detected by immunohistochemistry. All the datas are made of the SPSS17.0statistical software. The results are expressed as mean-±SD. Statistical differences between two groups were evaluated using t test.The differences among the three groups were evaluated using variance analysis.Statistical significance was accepted at P<0.05.ResultsAlong with the experiment, the rats of the model group gained weight much slowlyer than the other two groups, and their urine volume increased and had coarse hair. After2weeks, the blood uric acid level in model group was174.9±13.8μmol/L,which was higher than the control group [92.5±24.8u mol/L]and treatment group[97.7±25.2μmol/L], the differences were sinifican.(P<0.05).While there was no sinificant difference between the control group and the treatment group(P>0.05). The rat model of chronic primary hyperuricemia renal damage was successfully established and the intervention is effective. The mean serum creatinine level of model group was20.8±7.5μmol/L, the control group was21.1±1.8u mol/L and the treatment group was25.9±2.5μmol/L. There was no significant difference in serum creatinine levels among the there groups (P>0.05). After4weeks, the blood uric acid of the model group was211.1+/-30.9μmol/L, which was higher than the control group[113.1±34.3u mol/L] and the treatment group[137.5±36.3μmol/L] respectively, the differences were significant(P<0.05).While there was no significant difference between the control group and the treatment group (P>0.05). There was no significant difference in serum creatinine levels among the there groups (P>0.05). At the end of the6th week, the serum creatinine level in model group was40.9±5.7μmol/L, which was higher than the control group [23.2±1.8μmol/L]and treatment group[25±2.2μmol/L],the differences were sinificant.(P<0.05).While there was no sinificant difference between the control group and the treatment group (P>0.05). The renal damage is obvious in the model group but there was no significant diference between the control group and the treatment group,which means the early intervention of hyperuricemia is effective for the prevention of kidney damage.The eye view of the renal tissue:The kidneys in control and treated group rats were dark red, which had smooth surfaces and normal morphology.The kidneys in model group rats were pale and the, the volume increased significantly.Renal interstitial fibrosis area of the model group were (15.92±1.89)%], which were significantly increased than the control group [(6.43±0.26)%] and the treatment group (6.28±0.37)%](P<0.05). The eNOS expression in renal tissuesof the model group were [(281±091)%], which were significantly lower than the normal control group [(09±1)%] and the benzbromarone treatment group [(8.11±129)%](P<0.05).The ET-1and HIF-1a expression were significantly higher than the normal control group and treatment group (P<0.05).ConclusionHyperuricemia can reduce the synthesis of eNOS but increase the production of ET-1in the renal interstitial vascular endothelial cells, thus affecting the endothelial function of renal interstitial vascular and leading to renal interstitial fibrosis through an mechanism of ischemia and hypoxia.