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The implication of NO, R0S and their interaction in the pathogenesis of peritoneal injury

NO、R0S及其相互作用在腹膜损伤发病机制中的意义

基本信息

批准号：
15590868
负责人：
SASAKI Tamaki
金额：
$ 1.79万
依托单位：
Kawasaki Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The implication of NO, ROS and their interaction in the pathogenesis of peritoneal injuryNO and ROS are important mediators of various pathophysiological processes in vascular diseases. In addition, peroxynitrite formed by the interaction of NO and superoxide anion (O^<2->) can cause tissue damage of proteins, including the peritoneal membrane. The effect of a high glucose concentration (HG group, 214mM) on rat culture mesothelial cells (MC) was investigated. nNOS and iNOS mRNAs were expressed in the MC, however, eNOS mRNA was not detected. Furthermore, upon exposure to HG, these mRNA synthesis also increased, Subsequently, the MC produced more ROS than the control, however, increased production of NO was not detected. Tetrahydrobiopterin (BH4) was suppressed ROS production in HG condition. These results suggest that the accelerated ROS production and diminished by NOS uncoupling were revealed under High glucose. Peritonitis model rats were prepared. Localization of NOSs was revealed b … More y immunohistochemical staining method. nNOS was weakly detected in the MC of the control rats, however, strong staining was in this model. The presence of iNOS and nNOS in infiltrative cells in this model was confirmed. These results confirmed the up-regulation of NOS isoform, however, diminished bioavailable NO by ROS. The unbalance of NO and ROS may cause the peritoneal injury.The Role Of Abnormal Iron Metabolism In The Development Of Oxidative Peritoneal InjuryThis study examined the role of abnormal iron metabolism in causing the development of oxidative peritoneal injury. Peritonitis model rats were prepared. Localisation of iron, ferritin, 8-hydroxydeoxyguanosine (8-OHdG : an indicator of oxidative DNA damage) and lipid peroxidation (4-hydroxynonenal : 4-HNE) was revealed by the immunohistochemical staining method. The presence of iron in infiltrative cells in this model was confirmed. Also, 8-OhdG was detected in the mesothelial cells and vascular walls of these rats, as was increased 4-HNE immnoreactivity. Furthermore, human peritoneal biopsy specimens from fifty patients with sclerosing peritonitis were exmained. Iron was not detected in the healthy control group. However, strong staining was observed in the submesothelial areas and vascular walls of the patients with sclerosing peritonitis. The presence of iron in infiltrative cells in peritonitis was confirmed. The oxygen radical generated by the abnormalities in iron metabolism is involved in oxidative stress in the peritoneum or in peritoneal vessels, and in promotion of arteriosclerosis. Less

NO、ROS及其相互作用在腹膜损伤发病机制中的意义NO和ROS是血管疾病各种病理生理过程的重要介质。此外，NO与超氧阴离子(O^2-)相互作用形成的过氧亚硝酸盐可引起蛋白质组织损伤，包括腹膜。研究了高葡萄糖浓度（HG组，214mM）对大鼠培养间皮细胞（MC）的影响。 nNOS 和 iNOS mRNA 在 MC 中表达，但未检测到 eNOS mRNA。此外，暴露于 HG 后，这些 mRNA 合成也增加。随后，MC 比对照产生更多的 ROS，但没有检测到 NO 产生的增加。四氢生物蝶呤 (BH4) 在 HG 条件下抑制 ROS 产生。这些结果表明，在高葡萄糖条件下，ROS 产生加速并因 NOS 解偶联而减少。制备大鼠腹膜炎模型。通过免疫组织化学染色方法揭示了 NOS 的定位。在对照大鼠的 MC 中检测到微弱的 nNOS，但在该模型中检测到强染色。证实了该模型中浸润细胞中 iNOS 和 nNOS 的存在。这些结果证实了 NOS 异构体的上调，然而，ROS 减少了生物可利用的 NO。 NO和ROS的不平衡可能导致腹膜损伤。铁代谢异常在氧化性腹膜损伤发生中的作用本研究探讨了铁代谢异常在引起氧化性腹膜损伤发生中的作用。制备大鼠腹膜炎模型。通过免疫组织化学染色方法揭示了铁、铁蛋白、8-羟基脱氧鸟苷（8-OHdG：氧化DNA损伤的指标）和脂质过氧化（4-羟基壬烯醛：4-HNE）的定位。证实了该模型中浸润细胞中铁的存在。此外，在这些大鼠的间皮细胞和血管壁中检测到 8-OhdG，4-HNE 免疫反应性也增加。此外，还对来自 50 名硬化性腹膜炎患者的人类腹膜活检标本进行了检查。在健康对照组中未检测到铁。然而，在硬化性腹膜炎患者的间皮下区域和血管壁中观察到强染色。证实腹膜炎浸润细胞中存在铁。铁代谢异常产生的氧自由基参与腹膜或腹膜血管的氧化应激，并促进动脉硬化。较少的