特异性环加氧酶2抑制剂对肾大部切除大鼠肾脏的保护作用  

Renoprotective effect of specific cyclooxygenase-2 inhibitor on rats with 5/6 nephrectomy

作　　者：孔维信[1] 顾勇[1] 杨海春[1] 马骥[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内科,上海200040

出　　处：《中华肾脏病杂志》2002年第1期29-33,共5页Chinese Journal of Nephrology

基　　金：教育部博士点基金;上海市教育委员会曙光计划;复旦大学研究生创新基金(CQF151802)

摘　　要：目的 探讨特异性环加氧酶（ＣＯＸ）－２抑制剂（ｒｏｆｅｃｏｘｉｂ）对５／６肾切除大鼠肾脏病变的保护作用。方法 大鼠随机分为 ４组，１假手术组，Ⅱ肾切除（ＳＮＸ）组，皿 ＳＮＸ＋ｒｏｆｅｃｏｘｉｂ组，Ⅱ ＳＮＸ＋蚓哚美辛组。６周后检测大鼠血压、肾功能、尿蛋白及尿血栓烷Ｂ。（ＴＸＢ_２），观察肾组织病理改变，并应用ＲＴ－ＰＣＲ的方法检测肾皮质内ＴＧＦ－βｍＲＮＡ的表达；免疫沉淀方法检测ＴＧＦ－β１蛋白质的表达。结果ｒｏｆｅｃｏｘｉｂ组大鼠蛋白尿水平较ＳＮＸ组显著降低（Ｐ＜０．０５）；肾小球硬化及肾小球基底膜增生程度比ＳＮＸ组明显减轻（Ｐ＜０．０５）；肾皮质ＴＧＦ－βｒｍ ＲＮＲ及蛋白质表达水平较ＳＮＸ组分别下调４０．８２％（Ｐ＜０．０１）和５６．８４％（Ｐ＜０．００１）。吲跺美辛组大鼠蛋白尿水平虽较ＳＮＸ组降低，肾皮质ＴＧＦ－β１ｍＲＮＡ及其蛋白质的表达水平较ＳＮＸ组分别下调１６．４２％和１５ ．７６％（Ｐ＞０．０５），但均无统计学意义；肾小球硬化虽较ＳＮＸ组轻，但肾间质纤维化程度较ＳＮＸ组加重。结论 特异性ＣＯＸ－２抑制剂对５／６肾大部切除大鼠肾脏病变有部分保护作用。Objective To observe the renoprotective effect of specific cyclooxygenase-2 inhibitor (rofecoxib) on rats with 5/6 nephrectomy. Methods The rats were randomly assigned to following groups: sham-operation, nephrectomy(SNX), SNX treated with rofecoxib( 10 mg· kg^(-1)· d^(-1), SNX treated with indomethacin (2 mg· kg^(-1)· d^(-1) . The blood pressure, renal function as well as urinary protein and thromboxane B_2 were measured at the 6th week after operation, and the mRNA expression of TGF-β1 was detected by RT-PCR. Immunoprecipitation was used to examine the expression of TGF-1β. Results The level of proteinuria in rofecoxib group [(58. 8 ±14. 8) mg/d] was significantly less than that of SNX group [(101.7±28.35) mg/d], (P <0.05) . Rofecoxib treatment also significantly reduced the percentage of glomeruli exhibiting segmental or global sclerosis after 6 weeks. Furthermore, the mRNA and protein expression of TGF-β1 in rofecoxib group were diminished by approximately 40. 82% (P <0. 01) and 56. 84 (P <0.001), respectively. However, the level of proteinuria in indomethacin group [(78. 1 ±13. 1 )mg/d] was slightly less than that of SNX group. Indomethacin treatment also reduced the percentage of glomeruli exhibiting segmental or global sclerosis, but deteriorated interstitial fibrosis. The mRNA and protein expression of TGF-βl in indomethacin group were diminished by approximately 16. 42% and 15. 76% respectively ( P > 0. 05) . Conclusions Specific COX-2 inhibitor rofecoxib has a renoprotective effect on 5/6 nephrectomized rats. Further studies are required to determine the mechanism by which COX-2 inhibition is renoprotective.

关 键 词：肾切除术 转化生长因子Β1 特异性COX-2抑制剂 

分 类 号：R692.02[医药卫生—泌尿科学]