Decreased renal heme oxygenase-1 expression contributes to decreased renal function during cirrhosis.
Decreased renal heme oxygenase-1 expression contributes to decreased renal function during cirrhosis.
复制标题
DOI：
10.1152/ajprenal.00363.2001
复制
发表时间：
2002-11
期刊：
影响因子：
--
通讯作者：
Motoaki Miyazono;C. Garat;K. Morris;E. P. Carter
中科院分区：
文献类型：
--
作者：
Motoaki Miyazono;C. Garat;K. Morris;E. P. Carter
血红素加氧酶（HO）是血红素降解的限速酶，催化血红素分子氧化裂解为胆绿素、一氧化碳和铁。本研究旨在探讨HO-1在肝硬化肾功能不全发病机制中的作用。采用胆总管结扎法（CBDL）建立大鼠胆汁性肝硬化模型。手术后2周和5周对动物进行研究。在CBDL大鼠肾脏中，HO-1蛋白表达在2 wk时略有增加，但在5 wk时消失。此外，我们在组织学上证实，在5周龄CBDL大鼠的肾小管和小叶间小动脉中HO-1的表达受到抑制。相反，肝脏中HO-1的表达强烈增加。与肝硬化和肾功能不全的发展相一致，与假手术对照组相比，CBDL大鼠的平均动脉压（MAP）、肾小球滤过率（GFR）和肾血流量（RBF）降低。在假手术大鼠中，用选择性HO抑制剂锌原卟啉治疗显著降低GFR和RBF至与CBDL大鼠中测量的值相似的值，而不降低MAP。总之，肾HO-1表达下降有助于恶化肾功能和血流动力学在肝硬化。这一发现为肝硬化肾功能不全的病理生理学提供了新的机制。
Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, catalyzing the oxidative cleavage of heme molecules to biliverdin, carbon monoxide, and iron. The present study was designed to investigate the role of HO-1 in the pathogenesis of renal dysfunction during cirrhosis. Biliary cirrhosis was induced in rats by common bile duct ligation (CBDL). Animals were studied 2 and 5 wk after surgery. In kidney from CBDL rats, HO-1 protein expression increased slightly at 2 wk but was abolished at 5 wk. In addition, we confirmed histologically that HO-1 expression was suppressed in renal tubules and interlobular arterioles in 5-wk-old CBDL rats. Conversely, HO-1 expression in liver was strongly increased. Consistent with the development of cirrhosis and renal dysfunction mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal blood flow (RBF) were decreased in CBDL rats compared with sham-operated controls. In sham rats, treatment with the selective HO inhibitor zinc protoporphyrin markedly decreased GFR and RBF to values similar to those measured in CBDL rats without decreasing MAP. In conclusion, decreased renal HO-1 expression contributes to deteriorated renal function and hemodynamics during cirrhosis. This finding provides a novel mechanism for the pathophysiology of renal dysfunction during cirrhosis.