| Co-Investigator(Kenkyū-buntansha) |
KASHIHARA Naoki Kawasaki Medical School, Medicine, Professor, 医学部, 教授 (10233701)
SHINDOH Akihisa Kawasaki Medical School, Medicine, Assistant Professor, 医学部, 講師 (00278920)
HORIKE Hideyuki Kawasaki Medical School, Medicine, Assistant Professor, 医学部, 講師 (10289150)
MOCHIZUKI Seiichi Kawasaki Medical College, Clinical Engineering, Associate Professor, 臨床工学科, 助教授 (60259596)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
The implication of NO, ROS and their interaction in the pathogenesis of peritoneal injury
NO 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
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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 Injury
This 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
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