目的:探讨大鼠高尿酸血症肾损伤与沉默信息调节因子1（SIRT1）和内皮型一氧化氮合酶（eNOS）的关系。方法:将6周龄健康雄性Sprague-Dawley大鼠32只按随机数字表法分为对照组、模型A组（氧嗪酸钾建模）、模型B组（氧嗪酸钾联合尿酸建模）和白藜芦醇组，每组8只，实验共12周。动态监测血尿酸和胱抑素C水平，第12周加测血肌酐和尿素氮水平并取大鼠肾脏，采用免疫组化、实时荧光定量逆转录PCR（RT-qPCR）和Western印迹法测定肾组织SIRT1和eNOS的表达部位及表达量，α-平滑肌肌动蛋白的免疫组化联合Masson染色共同评估肾纤维化程度，HE染色观察肾脏病理变化。结果:第12周，模型A组和模型B组血尿酸水平均高于对照组［（316±43）μmol/L、（297±40）μmol/L比（118±44）μmol/L，均n P<0.05］；模型A组、模型B组和白藜芦醇组胱抑素C水平均高于对照组［（156±20）ng/ml、（143±29）ng/ml、（128±26）ng/ml比（62±18）ng/ml，均n P<0.05］；模型A组和模型B组血肌酐水平均高于对照组［（68.5±10.3）μmol/L、（64.5±13.9）μmol/L比（43.2±10.6）μmol/L，均n P<0.05］；与模型A组相比，白藜芦醇组血尿酸、胱抑素C和血肌酐水平均降低（均n P<0.05）。肾脏SIRT1/eNOS的免疫组化、RT-qPCR和Western印迹结果显示，与正常组相比，模型A组和模型B组表达均受抑制，白藜芦醇组表达未见明显抑制。大鼠肾脏镜下观察显示，对照组大鼠肾组织未见明显异常；模型A组和模型B组均出现肾脏炎细胞聚集和细胞水肿，间质纤维化明显；白藜芦醇组肾损伤较模型A组明显改善。n 结论:高尿酸血症可能通过抑制SIRT1/eNOS的表达造成肾损伤。“,”Objective:To investigate the association of hyperuricemia-induced renal damage with sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) in rats.Methods:Using the random number table method, 32 Sprague-Dawley rats were randomly divided into 4 groups: control group, model A group (the model was generated using oxonic acid potassium salt alone), model B group (hyperuricemia model was generated using oxonic acid potassium salt combined with uric acid) and resveratrol group, with 8 rats in each group. The experiment lasted 12 weeks. Serum uric acid and cystatin C levels were monitored regularly. In week 12, serum creatinine and urea nitrogen levels were measured, and the kidneys were extracted. The expression of SIRT1 and eNOS in renal tissues was measured and determined by immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. Immunohistochemistry of alpha-smooth muscle actin combined with Masson staining was employed to evaluate the degree of renal fibrosis, and pathological changes were observed based on hematoxylin and eosin staining.Results:In week 12, the uric acid levels in both the model A and model B groups were higher than those in the control group [(316±43) μmol/L, (297±40) μmol/L vs (118±44) μmol/L, both n P<0.05]. The levels of cystatin C in the model A, model B, and resveratrol groups were all higher than those in the control group [(156±20) ng/ml, (143±29) ng/ml, (128±26) ng/ml vs (62±18) ng/ml, alln P<0.05]. Creatinine levels were higher in the model A and model B groups than those in the control group [(68.5±10.3) μmol/L, (64.5±13.9) μmol/L vs (43.2±10.6) μmol/L, bothn P<0.05]. The levels of uric acid, cystatin C and creatinine in the resveratrol group were lower than those in the model A group (alln P<0.05). Immunohistochemistry, RT-qPCR, and Western blotting for renal SIRT1 and eNOS showed that the expression in the model A and model B groups was inhibited, while the expression in the resveratrol group was not significantly inhibited, compared with that in the control group. Microscopically, obvious abnormalities were not found in the renal tissue of the control group. Renal inflammatory cell aggregation and edema occurred, and interstitial fibrosis was obvious in both the model A and model B groups, while these lesions in the resveratrol group were significantly improved.n Conclusions:Hyperuricemia may cause renal injury by inhibiting the expression of SIRT1 and eNOS.