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Acute upregulation of COX-2 by renal artery stenosis.

机译:肾动脉狭窄对COX-2的急性上调。

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This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible causal relationship between the changes of COX-2 and of renin expression, clipped rats were treated with the COX-2 blocker celecoxib (40 mg. kg(-1). day(-1)). This treatment, however, did not change renin mRNA either in the clipped or in the contralateral intact kidney. Our findings indicate that renal artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin expression during renal hypoperfusion.
机译:这项研究旨在表征急性肾动脉狭窄对近肾小管中环氧合酶2(COX-2)和肾素表达的影响。为了这个目的,雄性Sprague-Dawley大鼠接受了左肾动脉夹,并测定了COX-2 mRNA,COX-2免疫反应性,血浆肾素活性和肾素mRNA水平。截短后6 h,截短肾脏黄斑区的COX-2 mRNA和COX-2免疫反应性增加,截短后1-2天达到最大表达。尽管血浆肾素活性的值在所有检查的时间点都显着升高,但剩余的肾素mRNA水平在6小时后没有变化,然后在剪后1-2天增加到最大值。在对侧完整肾脏中,肾素mRNA和COX-2免疫反应性降至其正常值的约50%。为了研究COX-2和肾素表达之间可能存在的因果关系,用COX-2阻断剂塞来昔布(40 mg。kg(-1)。day(-1))对截短的大鼠进行治疗。然而,这种治疗无论是在切除的还是对侧完整的肾脏中都没有改变肾素的mRNA。我们的发现表明,肾动脉狭窄会引起同侧急性肾小球上皮COX-2表达的急性上调,而对侧则引起下丘脑COX-2表达的下调。塞来昔布对肾素基因表达缺乏作用不支持在肾脏低灌注期间控制COX-2衍生前列腺素直接介导功能的概念。

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