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罗非昔布对单侧输尿管梗阻大鼠肾间质纤维化的改善作用
Renal protective effect of specific cyclooxygenase-2 inhibitor rofecoxib on obstructive nephropathy
【摘要】 目的:观察选择性环氧合酶2抑制剂罗非昔布对单侧输尿管梗阻大鼠肾间质纤维化的改善作用。方法:24只Wistar大鼠随机分成对照组(C组)、单侧输尿管梗阻(UUO)手术组(U组)及罗非昔布治疗组(R组),每组8只。U组和R组制作UUO模型,C组为假手术对照组。术前24h及术后以灌胃方式给药,R组给予罗非昔布(10mg·kg-1·d-1),C组和U组给予等量生理盐水,1次/d,共2周。放射免疫法测定尿TXB2浓度。免疫组化方法检测术后2周肾组织中TGFβ1、COX2的表达,并用硝酸还原酶法测定肾皮质组织中NO含量。结果:与C组相比,U组及R组尿TXB2水平、COX2、TGFβ1表达、NO含量均增高(P<0.05),与U组相比,R组尿TXB2水平、COX2、TGFβ1表达、NO含量均降低(P<0.05)。结论:罗非昔布可通过抑制COX2活性、下调TGFβ1的表达,抑制NO的合成等,从而延缓UUO大鼠肾间质纤维化的进展。
【Abstract】 Aim: To observe the renal protective effect of specific cyclooxygenase-2 inhibitor (refecoxib) on obstructive nephropathy.Methods:Twenty-four Wistar rats were randomly assigned to groups C, U, and R,Group U and group R were established unilateral ureteral obstraction (UUO) model,and group R was treated with rofecoxib (10 mg/(kg·d)).Group C was sham-operation group.Immunohistochemistry was used to investigate the expression of COX-2 and TGF-β1 after 2 weeks. The content of NO in renal cortex tissue was measured by enzymatic reaction test.Urine TXB2 was determined,too.Results: In comparison with sham-operation group ,the expression of COX-2,TGF-β1,NO content, and TXB2 of group U and group R were markedly increased(P<0.05). Compared with group U, the expression of COX-2, TGF-β1,content of NO and TXB2 in group R decreased(P<0.05). Conclusion: Rofecoxib has protective effect on the kidney by downregulating the expression of COX-2,TGF-β1 and the content of NO,which might alleviate the renal interstitial fibrosis after UUO.
【Key words】 cyclooxygenase; unilateral ureteral obstruction; rofecoxib; transforming growth factor-β1; nitric oxide;
- 【文献出处】 郑州大学学报(医学版) ,Journal of Zhengzhou University(Medical Sciences) , 编辑部邮箱 ,2006年03期
- 【分类号】R96
- 【被引频次】2
- 【下载频次】66