Kömhoff M, Jeck N D, Seyberth H W, Gröne H J, Nüsing R M, Breyer M D
Division of Nephrology, Departments of Medicine and Molecular Physiology and Biophysics, Veterans Administration Medical Center, and Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Kidney Int. 2000 Dec;58(6):2420-4. doi: 10.1046/j.1523-1755.2000.00425.x.
Bartter-like syndrome (BLS) is a heterogeneous set of congenital tubular disorders that is associated with significant renal salt and water loss. The syndrome is also marked by increased urinary prostaglandin E2 (PGE2) excretion. In rodents, salt and volume depletion are associated with increased renal macula densa cyclooxygenase-2 (COX-2) expression. The expression of COX-2 in human macula densa has not been demonstrated. The present studies examined whether COX-2 can be detected in macula densa from children with salt-wasting BLS versus control tissues.
The intrarenal distribution of COX-2 protein and mRNA was analyzed by immunohistochemistry and in situ hybridization in 12 patients with clinically and/or genetically confirmed BLS. Renal tissue rejected for transplantation, from six adult patients not affected by BLS, was also examined.
The expression of COX-2 immunoreactive protein was observed in cells of the macula densa in 8 out 11 patients with BLS. In situ hybridization confirmed the expression of COX-2 mRNA in the macula densa in 6 out of 10 cases. COX-2 protein was also detected in the macula densa in a patient with congestive heart failure. The expression of COX-2 immunoreactive protein was not observed in cells associated with the macula densa in kidneys from patients without disorders associated with hyper-reninemia.
These studies demonstrate that COX-2 may be detected in the macula densa of humans. Since macula densa COX-2 was detected in cases of BLS, renal COX-2 expression may be linked to volume and renin status in humans, as well as in animals.
巴特综合征样综合征（BLS）是一组异质性先天性肾小管疾病，与大量肾盐和水分流失有关。该综合征的特点还包括尿前列腺素E2（PGE2）排泄增加。在啮齿动物中，盐和容量耗竭与肾致密斑环氧化酶-2（COX-2）表达增加有关。尚未证实COX-2在人类致密斑中的表达。本研究检测了在失盐型BLS患儿的致密斑与对照组织中是否能检测到COX-2。
采用免疫组织化学和原位杂交技术分析了12例临床和/或基因确诊的BLS患者肾内COX-2蛋白和mRNA的分布。还检查了6例未受BLS影响的成年患者被拒绝移植的肾组织。
11例BLS患者中有8例在致密斑细胞中观察到COX-2免疫反应蛋白的表达。原位杂交证实10例中有6例致密斑中COX-2 mRNA表达。在1例充血性心力衰竭患者的致密斑中也检测到COX-2蛋白。在无高肾素血症相关疾病患者的肾中，未在与致密斑相关的细胞中观察到COX-2免疫反应蛋白的表达。
这些研究表明，在人类致密斑中可能检测到COX-2。由于在BLS病例中检测到致密斑COX-2，肾COX-2表达可能与人类以及动物的容量和肾素状态有关。
