Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice
Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice
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DOI：
10.1159/000121357
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Makino, Hirofumi
中科院分区：
文献类型：
--
作者：
Fukuoka, Naomi;Sugiyama, Hitoshi;Makino, Hirofumi
背景：腹膜纤维化是导致腹膜透析患者腹膜功能丧失的主要并发症。然而，尚未研究过氧化氢酶耗竭对腹膜纤维化的影响。研究方法：通过每隔一天腹膜内注射葡萄糖酸氯己定（CG）持续14天，在纯合型无丙氨酸血症突变小鼠或对照野生型小鼠中研究了过氧化氢酶缺乏对进行性腹膜纤维化的影响。结果如下：CG注射导致腹膜变厚，反映了腹膜纤维化伴间质I型胶原积聚、脂质过氧化产物（4-羟基-2-壬烯醛和4-羟基-2-己烯醛）腹膜沉积以及第14天两组小鼠腹膜液中8-羟基-2 '-脱氧鸟苷水平升高。然而，这些变化的程度，在acatalasemic小鼠显着高于野生型小鼠。过氧化氢酶活性的水平仍然很低，在acatalasemic腹膜谷胱甘肽过氧化物酶的补偿上调，但与CG注射小鼠的超氧化物歧化酶活性的上调不足。结论：因此，无酸酶血症加剧氧化剂组织损伤并诱导腹膜发展为不可逆的纤维化，这是腹膜透析的最重要并发症。这项研究表明，过氧化氢酶在小鼠腹膜纤维化模型中对氧化剂介导的腹膜损伤的防御中起着至关重要的作用。版权所有（C）2008 S. Karger AG，巴塞尔。
Background: Peritoneal fibrosis is a major complication leading to the loss of peritoneal function in patients undergoing peritoneal dialysis. However, the effect of catalase depletion on peritoneal fibrosis has not yet been investigated. Methods: The impact of catalase deficiency on progressive peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 14 days. Results: The CG injections resulted in a thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of interstitial type I collagen, peritoneal deposition of lipid peroxidation products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of 8-hydroxy-2'-deoxyguanosine in peritoneal fluid in both mouse groups on day 14. The extent of these changes, however, was significantly higher in acatalasemic mice than in wild-type mice. The level of catalase activity remained low in the acatalasemic peritoneum without the compensatory upregulation of glutathione peroxidase, but with an insufficient upregulation of superoxide dismutase activity in CG-injected mice. Conclusions: Acatalasemia, therefore, exacerbates oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis which is the most important complication of peritoneal dialysis. This study suggests that catalase plays a crucial role in the defense against oxidant-mediated peritoneal injury in a mouse peritoneal fibrosis model. Copyright (C) 2008 S. Karger AG, Basel.