Matsuyama M, Nakatani T, Hase T, Kawahito Y, Sano H, Kawamura M, Yoshimura R
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Transplant Proc. 2004 Sep;36(7):1939-42. doi: 10.1016/j.transproceed.2004.08.054.
Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils as well as the actions of inflammatory cytokines. However, few reports address cyclooxygenases (COXs) and lipoxygenases (LOXs). We researched the expression of COXs (COX-1 and COX-2) and LOXs (5-LOX and 12-LOX) in rat renal I/R injury. The right kidney of male Lewis rats was excised, and the left renal artery and vein clamped for a 90-minute ischemia time. Rats were humanely killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. COX and LOX expressions were studied using immunohistostaining. COX-2 and LOX expressions were observed only on endothelial cells of normal kidney. From 1.5 to 5 hours after reperfusion, COX-2 and LOXs expressions gradually intensified on endothelial cells. COX-2 and LOXs expression were most intense on endothelial cells at 5 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed. Thus, at 12 hours after reperfusion, COX-2 and LOXs expressions on endothelial cells became weaker. However, COX-1 expression was not different at every time after reperfusion. COX-2 and LOXs were expressed in a rat model showing renal I/R injury. Several hours after the maximum of COX-2 and LOXs expressions, the maximal renal I/R injury was observed. These results suggest a relationship between COX-2 and LOXs expressions and renal I/R injury.
近期关于缺血再灌注(I/R)损伤的研究主要集中在中性粒细胞的功能以及炎性细胞因子的作用上。然而,很少有报告涉及环氧化酶(COXs)和脂氧合酶(LOXs)。我们研究了COXs(COX-1和COX-2)和LOXs(5-LOX和12-LOX)在大鼠肾脏I/R损伤中的表达。切除雄性Lewis大鼠的右肾,夹闭左肾动脉和静脉90分钟以造成缺血。在再灌注后0、1.5、3、5和12小时对大鼠实施安乐死。使用免疫组织化学方法研究COX和LOX的表达。仅在正常肾脏的内皮细胞上观察到COX-2和LOX的表达。再灌注后1.5至5小时,内皮细胞上COX-2和LOXs的表达逐渐增强。再灌注后5小时,内皮细胞上COX-2和LOXs的表达最为强烈。再灌注12小时后,坏死扩展至整个缺血肾脏,几乎所有肾小管上皮细胞均被破坏。因此,再灌注12小时时,内皮细胞上COX-2和LOXs的表达变弱。然而,再灌注后各个时间点COX-1的表达并无差异。在大鼠肾脏I/R损伤模型中检测到COX-2和LOXs的表达。在COX-2和LOXs表达达到峰值数小时后,观察到最大程度的肾脏I/R损伤。这些结果提示COX-2和LOXs的表达与肾脏I/R损伤之间存在关联。