别嘌醇对尿酸性肾病大鼠肾功能的影响

Effect of allopurinol on the renal function of urinary acid nephropathy rats

目的研究别嘌醇治疗尿酸性肾病大鼠对其肾功能及肾组织肿瘤坏死因子-α(TNF-α)蛋白表达的影响。方法将54只SD大鼠随机分为模型组及实验组,各27只,以200 mg·kg^-1腺嘌呤联合250 mg·kg^-1乙胺丁醇连续灌胃2周构建尿酸性肾病大鼠模型,另选26只SD大鼠正常饲养作为对照组。建模成功后实验组大鼠灌胃30 mg·kg^-1·d^-1别嘌醇,模型组及对照组灌胃等量生理盐水,连续干预3周。以苏木精-伊红(HE)染色及Masson染色观察肾组织病理损伤及肾间质纤维化程度,比较各组大鼠尿酸(UA)含量、24 h尿蛋白定量(24 h UPQ)及肾功能指标含量变化;以免疫组化法检测肾组织TNF-α蛋白表达情况。结果对照组、模型组及实验组肾组织病理学评分分别为(0.15±0.02),(2.61±0.45),(1.02±0.33)分,肾间质纤维化(RIF)指数分别为(21.03±1.35)%,(59.27±4.68)%,(29.61±2.05)%,UA含量分别为(79.65±5.41),(251.31±19.38),(176.08±15.69)μmol·L^-1,血清尿素氮(BUN)含量分别为(8.13±2.01),(29.74±2.25),(10.31±2.69)mmol·L^-1,血清肌酸酐(SCr)含量分别为(69.28±10.41),(125.97±13.98),(98.65±11.25)μmol·L^-1,肾组织TNF-α蛋白阳性细胞百分比分别为(26.23±2.01)%,(85.14±6.98)%,(41.25±3.24)%,差异均有统计学意义(均P<0.05)。结论别嘌醇可有效改善尿酸性肾病大鼠肾组织病理损伤及肾间质纤维化损伤,恢复其肾功能,其作用机制可能与显著下调肾组织TNF-α蛋白表达相关。

Objective To explore the effect of allopurinol on the renal function and renal tissue tumor necrosis factor-α(TNF-α)protein expression of urinary acid nephropathy rats.Methods Forty-four cases SD rats were divided randomly into model group and test group,27 cases in each group,they were built urinary acid nephropathy rat model by intragastric administrated 200 mg·kg^-1 adenine combined with 250 mg·kg^-1 ethambutol continuously of 2 weeks,another 26 cases of normal breeding SD rats were divided into control group.After successfully modeling,rats in test group were intragastric administrated 30 mg·kg^-1·d^-1 allopurinol,model group and control group were intragastric administrated the same amount of normal saline.All groups were intervented for 3 weeks.The renal pathology morphology and renal interstitial fibrosis damage degree were observed by hematoxylin eosin(HE)staining and Masson staining respectively;the changes of uric acid(UA),24 h urine protein quantity(24 hUPQ)contents and renal function indexes of rats in each group were compared;the renal tissue TNF-αprotein expression was detected by immunohistochemistry.Results The renal histopathological scores in control group,model group and test group were(0.15±0.02),(2.61±0.45),(1.02±0.33)scores,renal interstitial fibrosis indexes were(21.03±1.35)%,(59.27±4.68)%,(29.61±2.05)%,UA contents were(79.65±5.41),(251.31±19.38),(176.08±15.69)μmol·L^-1,serum blood urea nitrogen(BUN)contents were(8.13±2.01),(29.74±2.25),(10.31±2.69)mmol·L^-1 respectively;serum serum creatinine contents were(69.28±10.4),(125.97±13.98),(98.65±11.25)μmol·L^-1,renal tissue TNF-αprotein positive cell proportions were(26.23±2.01)%,(85.14±6.98)%,(41.25±3.24)%,all with significant difference(all P<0.05).Conclusion Allopurinol can improve the renal pathological damage and renal interstitial fibrosis damage of urinary acid nephropathy rats effectively,restore the renal function of rats,and the action mechanism may be associated with down-regulation of renal tissueTNF-αprotein expression significantly.