基础医学与临床 ›› 2019, Vol. 39 ›› Issue (5): 720-725.

• 研究论文 • 上一篇    下一篇

氯沙坦钾下调尿酸性肾纤维化大鼠肾小管上皮细胞尿酸转运蛋白-1的表达

卢守燕,马志刚,黄军悦,李莹屏,黄文辉   

  1. 甘肃省人民医院
  • 收稿日期:2018-04-12 修回日期:2018-07-23 出版日期:2019-05-05 发布日期:2019-04-24
  • 通讯作者: 黄文辉 E-mail:huangwh9966@163.com

Losartan potassium down-regulates the expression of uric acid transporter -1 in renal tubular epithelial cells of rats with uric acid renal fibrosis

  • Received:2018-04-12 Revised:2018-07-23 Online:2019-05-05 Published:2019-04-24

摘要: 目的 研究氯沙坦钾对高尿酸血症致尿酸性肾纤维化大鼠肾小管上皮细胞尿酸转运蛋白-1(URAT1)表达的影响。方法 将大鼠随机分为正常组、模型组(以腺嘌呤100 mg/kg+乙胺丁醇250 mg/kg的混悬液灌胃造模)、氯沙坦钾低、中和高剂量灌胃治疗组(分别为25、50 和75 mg/kg?d)。各组于造模后第1、2、3和4周检测大鼠血尿酸、血肌酐、尿素氮、尿酸、尿肌酐和尿酸排泄分数,用HE和Masson染色法观察尿酸性肾纤维化大鼠病理变化,Western blot检测肾小管上皮细胞URAT-1蛋白的表达。结果 随着时间的延长,模型组大鼠血尿酸水平显著高于正常组(P<0.01),尿尿酸水平低于正常组(P<0.01);各治疗组血尿酸水平下降,尿尿酸水平升高,以高剂量组为著(P<0.05);模型组肾小管间质损伤指数明显高于同期正常组(P<0.05),氯沙坦钾干预后肾小管间质损伤指数明显降低(P<0. 05); URAT1蛋白表达在模型组各时间段升高(P<0. 05),且随着病理损害的进展呈现上升趋势,经氯沙坦钾干预后表达显著下降(P<0. 05)。结论 氯沙坦钾可能下调URAT1高表达,显著降低高尿酸血症大鼠的血尿酸水平。

关键词: 高尿酸血症,尿酸性肾纤维化,尿酸转运蛋白1,氯沙坦钾

Abstract: Objective To observe the effect of losartan potassium on the expression of Uric acid transporter1(URAT1) in renal epithelial cells of hyperuricemia rats with renal interstitial fibrosis. Methods The rats were randomly divided intonormal group,model group(it was administrated with adenine 100 mg/(kg?d) and Ethambutol 250 mg/(kg?d) by gastric gavage),losartan potassium low ,in and high (25、50 and75 mg/kg?d) dose treatment group.Serum uric acid, serum creatinine, urea nitrogen, urinary uric acid, urinary creatinine and uric acid excretion fraction were detected at 1, 2, 3and 4W after modeling. Pathological changes of uric acid renal fibrosis rats were observed by HE and Masson staining methods,and the protein expression of URAT-1 was detected in renal tubular epithelial cells by Western blot. Results With the extension of time, serum uric acid level of model group was significantly higher than that of normal group(P<0.01), uric acid level was lower than normal group(P<0.01), serum uric acid level decreased and uric acid level increased in the treatment group, The high dose group was the most obvious(P<0.05).The tubulointerstitial injury index in the model group was significantly higher than that in the normal group (P<0.05), and the tubulointerstitial injury index was significantly decreased after losartan potassium intervention (P<0.05) . The expression of URAT1 protein were up-regulated in the model group at each time period (P<0.05), and with the progress of pathological damage showed an upward trend, but decreased significantly in losartan potassium intervention groups(P<0.05). Conclusions  Losartan potassium may reduce the high expression of URAT1 and significantly reduce the level of serum uric acid in hyperuricemia rats.

Key words: hyperuricemia, Uric acid renal fibrosis, URAT1, losartan potassium