Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney
Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney
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DOI：
10.1152/ajprenal.00215.2004
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发表时间：
2005-04-01
影响因子：
4.2
通讯作者：
Agarwal, A
中科院分区：
文献类型：
--
作者：
Adin, CA;Croker, BP;Agarwal, A
血红素氧合酶-1（HO-1）作为对组织损伤的适应性和保护性反应而被诱导。HO-1将血红素降解为一氧化碳（CO）和胆绿素;后者然后转化为胆红素。这些反应产物具有强大的抗凋亡和抗氧化作用。通过给予微摩尔剂量的外源性CO或胆红素来操纵HO-1系统已在几个器官系统中进行，但尚未在肾脏中研究这些反应产物的剂量相关效应。本研究的目的是评估热缺血20分钟前1或10 μ M胆红素冲洗的有效性和剂量相关的保护作用。为了尽量减少与其他化学信使或器官系统的相互作用，我们选择使用一个孤立的，灌注大鼠肾脏模型与脱细胞，充氧灌注液。使用该模型，我们证明胆红素治疗导致缺血再灌注损伤（IRI）后肾血管阻力，尿量，肾小球滤过率，肾小管功能和线粒体完整性的显着改善。10 μ M胆红素剂量对器官活力的有益作用最为一致。我们的结论是，HO-1活性在IRI期间在肾脏中的保护作用介导的，至少部分，由胆红素和预处理与微摩尔剂量的胆红素可能提供一个简单而廉价的方法，以改善IRI后的肾功能。
Heme oxygenase-1 (HO-1) is induced as an adaptive and protective response to tissue injury. HO-1 degrades heme into carbon monoxide (CO) and biliverdin; the latter is then converted to bilirubin. These reaction products have powerful antiapoptotic and antioxidant effects. Manipulation of the HO-1 system by administration of micromolar doses of exogenous CO or bilirubin has been performed in several organ systems, but the dose-related effects of these reaction products have not been investigated in the kidney. The purpose of this study was to evaluate the efficacy and dose-related protective effects of 1 or 10 muM bilirubin flush before a 20-min period of warm ischemia. In an effort to minimize interactions with other chemical messengers or organ systems, we elected to use an isolated, perfused rat kidney model with an acellular, oxygenated perfusate. Using this model, we demonstrated that bilirubin treatment resulted in significant improvements in renal vascular resistance, urine output, glomerular filtration rate, tubular function, and mitochondrial integrity after ischemia-reperfusion injury (IRI). Beneficial effects on organ viability were achieved most consistently with a dose of 10 muM bilirubin. We conclude that the protective effects of HO-1 activity during IRI in the kidney are mediated, at least in part, by bilirubin and that pretreatment with micromolar doses of bilirubin may offer a simple and inexpensive method to improve renal function after IRI.