痛风定对尿酸性肾病大鼠肾脏肿瘤坏死因子-α、单核细胞趋化蛋白-1和细胞间黏附分子-1mRNA的影响

Effection of capsule tongfengding on tumor necrosis factor-α,monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 mRNA expression in hyperuricemic nephropathy rat

目的探讨痛风定对尿酸性肾病大鼠肾脏肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)和细胞间黏附分子-1(ICAM-1)mRNA的影响。方法将右侧肾脏切除手术后的40只大鼠随机分为4组:手术组、模型组(氧嗪酸钾750 mg/(kg·d))、别嘌呤醇组(氧嗪酸钾750 mg/(kg·d)+别嘌呤醇50 mg/(kg·d))、痛风定组(氧嗪酸钾750 mg/(kg·d)+痛风定500 mg/(kg·d))。实验期间定期检测血尿酸、尿素氮、肌酐水平和24 h尿蛋白定量,药物干预第8周结束时处死所有大鼠,留取肾脏组织,采用实时荧光定量聚合酶链式反应检测大鼠肾脏组织中TNF-α、MCP-1和ICAM-1 mRNA的表达。结果别嘌呤醇和痛定均有效降低血清尿酸水平(P<0.01),改善肾功能(P<0.05)。模型组大鼠肾脏组织TNF-α、MCP-1和ICAM-1明显高于手术组(P<0.01),别嘌呤醇和痛定均能减少氧嗪酸钾所致的TNF-α、MCP-1和ICAM-1表达升高(P<0.01)。结论 TNF-α、MCP-1和ICAM-1介导的炎症反应可能参与尿酸性肾脏病的进展过程,痛风定可能部分通过抑制尿酸所致的炎症反应而保护肾功能,延缓肾脏病的进展。

Objective To observe the effect of capsule tongfengding on tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1) and intercellular adhesion molecule- 1(ICAM-1) mRNA expression in hyperuricemic nephropathy rat.Methods One week after a right nephrectomy,40 rats were randomly divided into 4 groups:operation group,model group(oxonic acid kalium 750 mg/(kg·d)),allopurinol treatment group(oxonic acid kalium 750 mg/ (kg·d)+allopurinol 50 mg/(kg·d)),Tongfengding treatment group(oxonic acid kalium 750 mg/ (kg·d)+Tongfengding 500 mg/(kg·d)).Levels of serum uric acid,blood urea nitrogen,serum creatinine,urinary protein levels were measured every fortnight.Real-time quantitative polymerase chain reaction was used to detect the expression of TNF-α,MCP-1 and ICAM-1 in kidney at the end of study.Results Allopurinol and Tongfengding significantly reduced serum uric acid concentration(P &lt;0.01),and ameliorated the renal dysfunction(P &lt;0.05).Compared with operated rats,the expression of TNF-α,MCP-1 and ICAM-1 mRNA were increased in model group(P &lt;0.01).The administration of allopurinol or Tongfengding in rats resulted in lower TNF-α,MCP-1 and ICAM-1 mRNA expression(P &lt;0.01).Conclusion Tongfengding may retard the progression of uric acid induced renal injury via a mechanism partly linked to modulate TNF-α,MCP-1 and ICAM-1-mediated inflammation disease.