Inhibition of Nitric Oxide Synthase Reverses Permeability Changes in a Mouse Model of Acute Peritonitis
Inhibition of Nitric Oxide Synthase Reverses Permeability Changes in a Mouse Model of Acute Peritonitis
复制标题
抑制一氧化氮合酶可逆转急性腹膜炎小鼠模型的通透性变化
DOI：
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发表时间：
2005
影响因子：
2.8
通讯作者：
O. Devuyst
中科院分区：
文献类型：
--
作者：
J. Ni;Y. Cnops;R. McLoughlin;N. Topley;O. Devuyst
急性腹膜炎是腹膜透析最常见的并发症。以往的研究表明，一氧化氮（NO）在急性腹膜炎引起的渗透性变化和超滤丧失中起主要作用。在这项研究中，我们进一步研究了NO在大肠杆菌脂多糖（LPS）诱导的腹膜炎小鼠模型中的潜在作用。在对照和LPS处理的小鼠中使用补充或不补充NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）的7%葡萄糖透析液进行2小时腹膜平衡测试。在注射LPS后18小时，透析液中的NO代谢物水平最高。当时，与对照组相比，LPS诱导的急性腹膜炎表现为白细胞募集增加、腹腔内白细胞介素-6释放增加、小分子溶质的腹膜渗透性显著增加、钠筛分损失和超滤损失。在LPS处理的小鼠中添加L-NAME显著逆转渗透性改变，并防止NO代谢产物释放到透析液中。这些结果证实，增加NO介导的渗透性修改在急性腹膜炎，并说明小鼠模型的潜力，以调查调节腹膜通透性的分子机制。
Acute peritonitis is the most frequent complication of peritoneal dialysis. Previous studies have suggested a major role for nitric oxide (NO) in the permeability changes and loss of ultrafiltration induced by acute peritonitis. In this study, we further investigated the potential role of NO in a mouse model of peritonitis induced by Escherichia coli lipopolysaccharide (LPS). A 2-hour peritoneal equilibration test was performed in control and LPS-treated mice using 7% glucose dialysate supplemented or not with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The levels of NO metabolites in the dialysate were maximal 18 hours after LPS injection. At that time, acute peritonitis induced by LPS was reflected by an increased recruitment of leukocytes, an increased intraperitoneal release of interleukin-6, a significant increase in the peritoneal permeability for small solutes, a loss of sodium sieving, and a loss of ultrafiltration in comparison with controls. Addition of L-NAME in LPS-treated mice significantly reversed permeability modifications and prevented the release of NO metabolites into the dialysate. These results confirm that increased NO mediates permeability modifications during acute peritonitis, and illustrate the potential of mouse models to investigate the molecular mechanisms regulating peritoneal permeability.
影响因子：
6
作者：
Mahoney, E;Reichner, J;Albina, J
通讯作者：
Albina, J