Chou Shyan-Yih, Cai Hui, Pai David, Mansour Mervat, Huynh Paul
Department of Medicine, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA.
J Urol. 2003 Oct;170(4 Pt 1):1403-8. doi: 10.1097/01.ju.0000082964.24635.15.
The cyclooxygenase (COX) pathway is activated in unilateral ureteral obstruction (UUO), contributing to renal hemodynamic alterations in different regions of the kidney. After the release of 24-hour UUO cortical vasoconstriction occurs but medullary hyperemia is seen. We examined the expression of the 2 COX isoforms COX-1 and COX-2 in different regions of the kidney in rats subjected to UUO.
Clearance experiments were performed after ureteral obstruction release in rats with 24-hour UUO or sham operated rats. COX-1 and COX-2 expression in the cortex and medulla were examined by Western blot analysis and immunohistochemistry.
After UUO release the glomerular filtration rate and renal plasma flow were markedly lower in post-obstructed kidneys than in contralateral kidneys or in kidneys in sham operated rats (p <0.001). Western blot analysis showed that COX-2/beta-actin in the cortex of the obstructed kidney was 0.28 +/- 0.02 densitometry units, significantly lower than 0.67 +/- 0.12 densitometry units in the contralateral unobstructed kidney. In contrast, COX-2/beta-actin in the outer and inner medullae of the obstructed kidney was 7.85 +/- 1.09 and 2.51 +/- 0.14 densitometry units, significantly greater than 3.03 +/- 0.22 and 0.66 +/- 0.14 densitometry units, respectively, in the contralateral unobstructed kidney. The expression of COX-1/beta-actin in the obstructed kidney was similar to that in the contralateral unobstructed kidney in the cortex and medulla.
Renal COX-2 expression is markedly altered in UUO. Decreased cortical expression of COX-2 and markedly increased expression in the medulla may contribute to disparate regional hemodynamic alterations in UUO.
环氧化酶（COX）途径在单侧输尿管梗阻（UUO）中被激活，导致肾脏不同区域的肾血流动力学改变。在解除24小时UUO后，皮质出现血管收缩，但髓质出现充血。我们研究了UUO大鼠肾脏不同区域中两种COX同工型COX-1和COX-2的表达。
对24小时UUO大鼠或假手术大鼠在输尿管梗阻解除后进行清除率实验。通过蛋白质印迹分析和免疫组织化学检查皮质和髓质中COX-1和COX-2的表达。
解除UUO后，梗阻侧肾脏的肾小球滤过率和肾血浆流量明显低于对侧肾脏或假手术大鼠的肾脏（p<0.001）。蛋白质印迹分析显示，梗阻侧肾脏皮质中COX-2/β-肌动蛋白为0.28±0.02光密度单位，明显低于对侧未梗阻肾脏的0.67±0.12光密度单位。相比之下，梗阻侧肾脏外髓和内髓中的COX-2/β-肌动蛋白分别为7.85±1.09和2.51±0.14光密度单位，明显高于对侧未梗阻肾脏的3.03±0.22和0.66±0.14光密度单位。梗阻侧肾脏皮质和髓质中COX-1/β-肌动蛋白的表达与对侧未梗阻肾脏相似。
UUO时肾脏COX-2表达明显改变。皮质中COX-2表达降低以及髓质中表达明显增加可能导致UUO中不同区域的血流动力学改变。
