摘要
目的 探索肾大部切除大鼠肾皮质环加氧酶2(cyclooxygenase,COX2)的表达及特异性COX2抑制剂罗 非昔布对其的影响。方法 将大鼠随机分为6组,每组6只:Ⅰ.假手术组(Sham组),Ⅱ.肾大部切除组(SNX 组),Ⅲ.SNX+罗非昔布组(Rof组),Ⅳ.SNX+吲哚美辛组(Ind组),V.SNX+氯沙坦组(Los组),Ⅵ.SNX+罗 非昔布+氯沙坦合用组(R+L组)。6周后检测大鼠尿蛋白与尿血栓烷素B2(TXB2)的排泄量,检测肾皮质血管 紧张素Ⅱ浓度,应用免疫组化、逆转录聚合酶链反应(RT-PCR)及Western blotting的方法检测COX2及COX1 mRNA及蛋白质的表达。结果 SNX组大鼠血压较Sham组显著升高,Los组及R+L组血压较SNX组明显降 低(P<0.01),而Rof组及Ind组血压与SNX组相比无显著差别(P>0.05)。与Sham组相比,SNX组大鼠尿蛋 白及肾皮质COX2的表达与尿TXB2排泄明显增多,COX1表达无明显变化,AngⅡ浓度明显增高。Rof组及R+ L组肾皮质COX2表达下调,尿'IX]吃排泄明显减少,(X)X1表达无明显变化,AreⅡ浓度降低。Ind组(X)X2及 COXl表达均下调,尿'IX]B2排泄明显减少;氯沙坦对(X)X2及COXl无明显影响。结论肾大部切除大鼠肾皮 质(X)X2的表达与尿'TXB2排泄明显增多,COXl表达无明显变化。特异性COX2抑制剂罗非昔布使ODX2的 表达下调.部分抑制肾素一血管紧张素系统的兴奋。
Purpose To investigate the regulation of cortical cyclooxygenase-2 expression in rats with subtotal renal ablation. Methods Rats were ran domly assigned to six groups with 6 animals in each group:sham-operated (Sham),subtotal renal ablation(SNX),SNX treated with rofecoxib(10 mg/kg·d-1), SNX treated with indomethacin(2 mg/kg·d-1) ,SNX treated with losartan(100 mg/kg·d-1) ,SNX treated with rofecoxib and losartan(R+L). The urinary protein and thromboxane B2 as well as cortical angiotensin Ⅱ were measured after six weeks. The expression of cortical COX2 and COX1 were detected by way of immunohistochemistry,RT-PCR and Western blotting. Results Systolic BP was significantly increased in group SNX 6 weeks after subtotal renal ablation. The increases in SBP were significantly blunted in group Los and group R+L(P<0.05),while SBP in group Rof and group Ind rats were not significantly different from that in SNX. The rats in group SNX manifested progressively increasing proteinuria (101.7±28.4)mg/d and COX2 expression and TXB2 excretion were significantly increased while COX1 expression remained undisturbed in comparison with those in Sham group.The level of angiotensin Ⅱ in cortex was in creased in group SNX. Rofecoxib significantly down-regulated COX2 expression accompanied with TXB2 excretion decreased while CDX1 expression remained undistubed. Indomethacin significantly decreased both of COX2 and CDX1. Conclusions COX2 expression and TXB2 excretion were significantly increased in rats with subtotal renal ablation while CDXl expression remained undistubed. Rofecoxib down-regulated COX2 expression and partly inhibited the activation of renal renin-angiotensin system.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2005年第1期13-17,i002,共6页
Fudan University Journal of Medical Sciences
基金
教育部博士点基金上海市教委曙光计划复旦大学研究生创新基金(CQF151802)
