特异性环氧合酶-2抑制剂对肾大部切除大鼠肾脏纤溶酶原激活物抑制剂-1表达的影响  

The effect of a specific cyclooxygenase-2 inhibitor on the expression of plasminogen activator inhibitor type 1 in rats with subtotal nephrectomy

作　　者：孔维信[1] 马骥[1] 顾勇[1] 杨海春[1] 左怡沁[1] 林善锬[1] 

机构地区：[1]复旦大学附属华山医院肾脏科,上海200040

出　　处：《上海医学》2002年第5期288-291,共4页Shanghai Medical Journal

基　　金：教育部博士点基金资助项目 ;上海市教委曙光计划 ;复旦大学研究生创新基金资助项目 (CQF15 180 2 )

摘　　要：目的　探讨特异性环氧合酶 2 (COX 2 )抑制剂 (Rofecoxib)对肾大部切除 (SNX)大鼠肾脏纤溶酶原激活物抑制剂 1(PAI 1)表达的影响。方法　大鼠随机分为 5组 :Ⅰ组为假手术组 ;Ⅱ组为SNX组 ;Ⅲ组为SNX+Rofecoxib组 ;Ⅳ组为SNX +吲哚美辛组 ;Ⅴ组为SNX +氯沙坦组。 6周后检测大鼠血压、肾功能、尿蛋白及尿血栓烷素B2 (TXB2 ) ,应用逆转录 聚合酶链反应 (RT PCR)法检测肾皮质内PAI 1mRNA的表达 ;采用免疫组织化学及WesternBlot法检测PAI 1蛋白质的表达。结果　Rofecoxib组大鼠尿蛋白水平较SNX组显著降低 (P<0 .0 5 ) ,肾小球硬化及肾小球基底膜增生程度较SNX组明显减轻 ,与氯沙坦组相近。Rofecoxib组肾皮质PAI 1mRNA及蛋白质表达水平分别较SNX组下调 40 .2 4%和 31.16 % (P <0 .0 1)。结论　特异性COX 2抑制剂可能通过部分抑制PAI 1基因的表达 ,减少细胞外基质的分泌并促进其降解 。Objective To investigate the effect of specific cyclooxygenase 2 inhibitor (Rofecoxib) on the expression of PAI 1 in rats with subtotal nephrectomy(SNX). Methods The rats were randomly divided into five groups: sham operation group; SNX group; SNX treated with Rofecoxib (10 mg·kg -1 ·d -1 ); SNX treated with indomethacin (2 mg·kg -1 ·d -1 ); SNX treated with losartan (100 mg·kg -1 ·d -1 ). The blood pressure, urinary protein and thromboxane B 2 were measured at the 6th week after operation, and the PAI 1 mRNA expression was detected by RT PCR. Its protein expression was determined by Western Blot and immunohistochemistry. Results The levels of proteinuria in Rofecoxib group [(58.8±14.8) mg/day] were significantly less than SNX group [(101.7±28.3) mg/day, P <0.05] and were comparable to those seen in losartan group. Rofecoxib also significantly reduced the percentage of glomerular sclerosis and basement membrane proliferation after 6 weeks. Furthermore, the expression of PAI 1 mRNA and protein in Rofecoxib group were down regulated by approximately 40.24% and 31.16% ( P <0.01), respectively. Conclusion Specific COX 2 inhibitor Rofecoxib may ameliorate progressive glomerular sclerosis by inhibiting partly the expression of PAI 1 mRNA and protein, and by decreasing the deposition of extracellular matrix and accelerating its degradation.

关 键 词：特异性环氧合酶-2抑制剂 肾大部切除术 纤溶酶原激活物抑制剂-1 肾小球硬化 动物模型 

分 类 号：R363[医药卫生—病理学]