Altered expression of COX-1, COX-2, and mPGES in rats with nephrogenic and central diabetes insipidus
Altered expression of COX-1, COX-2, and mPGES in rats with nephrogenic and central diabetes insipidus
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DOI：
10.1152/ajprenal.00114.2004
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发表时间：
2005-05-01
影响因子：
4.2
通讯作者：
Nielsen, S
中科院分区：
文献类型：
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作者：
Kotnik, P;Nielsen, J;Nielsen, S
前列腺素在肾脏盐和水的重吸收中起重要作用。PGE(2)是主要的肾前列腺素，被认为主要产生于肾内髓质（IM）。有迹象表明肾源性尿崩症（NDI）和中枢性尿崩症（CDI）的PGE(2)合成发生了改变。我们假设NDI和CDI大鼠肾脏中主要的PGE2合成酶环加氧酶1和2 （COX-1、COX-2）和膜相关PGE2合成酶（mPGES）的表达发生了改变。以锂给药4周的Wistar大鼠作为NDI模型。将NDI模型大鼠的一半额外脱水48 h，以内源性抗利尿激素缺乏的BB大鼠作为CDI模型。采用免疫印迹和免疫组织化学方法检测COX-1、COX-2和mPGES在IM、外髓质内条纹（ISOM）和皮质中的表达和定位。在锂诱导的NDI中，IM中COX-1、COX-2和mPGES的表达明显降低。在ISOM和皮质中，COX-1表达轻度降低，mPGES表达不变。COX-2在ISOM中未见表达，而在皮质中略有升高。与此相一致的是，黄斑中表达COX-2的细胞密度显著增加，表明COX-2在IM和皮质中的调节存在差异。NDI大鼠脱水后，IM间质细胞COX-2免疫标记明显升高，各肾区COX-1和mPGES表达无明显变化。DDAVP治疗BB大鼠6天后，IM中COX-1、COX-2和mPGES的表达显著增加。在皮层中，COX-1和mPGES的表达没有变化，而COX-2的表达下降。这些结果表明，在锂诱导的NDI中，IM中COX-1、COX-2和mPGES的表达显著降低。此外，CDI大鼠COX-1、COX-2和mPGES的表达也发生了重大变化。
Prostaglandins have an important role in renal salt and water reabsorption. PGE(2) is the main kidney prostaglandin and is thought to be mainly produced in the kidney inner medulla (IM). There are indications that PGE(2) synthesis in nephrogenic (NDI) and central (CDI) diabetes insipidus is altered. We hypothesize that the expression of the major PGE2 synthesis enzymes cyclooxygenases 1 and 2 (COX-1, COX-2) and membrane-associated PGE2 synthase (mPGES) is altered in the kidneys of rats with NDI and CDI. Wistar rats treated with lithium for 4 wk were used as the NDI model. One-half of the NDI model rats were additionally dehydrated for 48 h. Brattleboro ( BB) rats that lack endogenous antidiuretic hormone were used as the CDI model. Expression and localization of COX-1, COX-2, and mPGES in IM, inner stripe of outer medulla (ISOM), and cortex were determined by immunoblotting and immunohistochemistry. In lithium-induced NDI, expression of COX-1, COX-2, and mPGES was markedly decreased in IM. In ISOM and cortex, COX-1 expression was marginally reduced and mPGES expression was unaltered. COX-2 expression was undetected in ISOM and marginally increased in cortex. Consistent with this, the density of COX-2-expressing cells in macula densa was significantly increased, indicating differential regulation of COX-2 in IM and cortex. Dehydration of NDI rats resulted in a marked increase in COX-2 immunolabeling in IM interstitial cells, and there was no significant change in COX-1 and mPGES expression in any kidney zone. Treatment of DDAVP in BB rats for 6 days resulted in a markedly increased expression of COX-1, COX-2, and mPGES in IM. In the cortex, there were no changes in the expression of COX-1 and mPGES, whereas COX-2 expression was decreased. These results identify markedly reduced expression of COX-1, COX-2, and mPGES in IM in lithium-induced NDI. Furthermore, there were major changes in the expression of COX-1, COX-2, and mPGES in rats with CDI.