Mitochondria injuries of Peritoneal Mesothelial Cells induced by oxidative stress

氧化应激诱导腹膜间皮细胞线粒体损伤

• 批准号: 13671131
• 负责人: SASAKI Tamaki
• 金额: $ 0.9万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671131/
• 关键词: Peritoneum; Mesothelial cell; Oxidative stress; Mitochondria; Angiogenesis; Klotho mouse; 8-OHdG; 硬化性腹膜炎

Oxidative stress by reactive oxygen species (ROS) is thought to be involved in the pathogenesis of various diseases. The pathological effect of oxidative stress on the peritoneum was studied basically with 8- OHdG. Immunohistochemical staining of 8- OHdG was weakly detected in the mesothelial cells of the healthy control, whereas strong staining was observed in the mesothelial cells and vascular walls of patients with sclerosing peritonitis. The presence of 8- OHdG in infiltrative cells in peritonitis was confirmed. The 8- OHdG levels in CAPD solution increased in proportion to the duration of dialysis irrespective of age, and they were high in the patients with peritonitis. Thereforem the 8- OHdG level in CAPD solutions might possibly be used as a clinical marker of inflammttion of the peritoneum and impairment of mesothelial cellsSubsequently, the effect of a high glucose concentration (HG group, 214mM) on rat culture mesothelial cells was investigated. The ROS production was visuali … More zed and checked by Dichlorofluorescein diacetat. Upon exposure to HG, the mesothelial cells produced more ROS than those of the control group. These results suggest that the mitochondria were extremely vulnerable to oxidative stress because they were a major intracellular source of ROSNext, neoangiogenesis during acute peritonitis was investigated morphologically. Fluorescent Griffonia simplicifolia 1 lectin was used to visualize the pattern of capillaries in the peritoneum by laser scanning confocal microscopy. Branching anastomoses between the parallel parent capillaries formed an irregular lace- like meshwork rather than individual straight interconnections. In the peritonitis model rats, cell infiltration was recognized on the surface of the peritoneum, and some of these cells expressed CD34. Immunohistocemistry revealed expression of Flk-1, Flt-1, and Tie-2 in these cells. These results may represent a new and promising strategy for dealing with peritoneal dysfunction by clinical application to new vessel formation Less

由活性氧（ROS）引起的氧化应激被认为参与多种疾病的发病机制。用8- OHdG初步研究了氧化应激对腹膜的病理作用。免疫组织化学染色8- OHdG弱检测到健康对照的间皮细胞，而强染色观察到硬化性腹膜炎患者的间皮细胞和血管壁。证实腹膜炎浸润细胞中存在8- OHdG。CAPD溶液中8- OHdG水平随透析时间的延长而升高，与年龄无关，腹膜炎患者的8- OHdG水平较高。因此，CAPD液中8- OHdG水平可能作为腹膜炎症和间皮细胞损伤的临床指标。随后，研究了高糖（HG组，214 mM）对大鼠培养间皮细胞的影响。ROS的产生是直观的， ...更多信息 用二醋酸二氯荧光素进行检测。暴露于HG后，间皮细胞产生更多的ROS比对照组。这些结果表明，线粒体是非常脆弱的氧化应激，因为它们是一个主要的细胞内来源的ROS接下来，在急性腹膜炎的新血管生成进行了形态学研究。荧光Griffonia simplicifolia 1凝集素用于通过激光扫描共聚焦显微镜观察腹膜中毛细血管的图案。平行的母毛细血管之间的分支形成不规则的花边状网络，而不是单独的直线互连。在腹膜炎模型大鼠中，在腹膜表面上识别到细胞浸润，并且这些细胞中的一些表达CD 34。免疫组织化学显示这些细胞中Flk-1、Flt-1和Tie-2的表达。这些结果可能代表了一个新的和有前途的战略，处理腹膜功能障碍的临床应用，以新的血管形成

项目成果

Hideyuki Horike, et al: "Impaired Angiogenesis in the Development of Intersitital Fibrosis in the Progressive Renal Disease"J Am Soc Nephrol. 13: 164A. (2002)

Hideyuki Horike 等人：“进行性肾病间质纤维化发展中的血管生成受损”J Am Soc Nephrol。

Hideyuki Horike, et al.: "The Role of Mitochondria in the Angiogenesis for Repairing the Interstitial Iniuries"J Am Soc Nephrol. 13. 164A (2002)

Hideyuki Horike 等人：“线粒体在修复间质损伤的血管生成中的作用”J Am Soc Nephrol。

Hideyuki Horike, et al.: "The Role of Mitochondria in the Angiogenesis for Repairing the Interstitial Injuries"J Am Soc Nephrol. 13. 164A (2002)

Hideyuki Horike 等人：“线粒体在修复间质损伤的血管生成中的作用”J Am Soc Nephrol。

Hideyuki Horike, et al.: "Impaired Angiogenesis in the Development of Interstitial Fibrosis in the Progressive Renal Diseases"J Am Soc Nephrol. 13. 164A (2002)

Hideyuki Horike 等人：“进行性肾病中间质纤维化发展中的血管生成受损”J Am Soc Nephrol。

Tatsuo Fukushima, et al: "Accumulation of Oxidative DNA Damage and hOGGl Polymorphism are Correlated with Pathogenesis of Diabetic Nephropathy"J Am Soc Nephrol. 12: 146A. (2001)

Tatsuo Fukushima 等人：“氧化 DNA 损伤和 hOGG1 多态性的积累与糖尿病肾病的发病机制相关”J Am Soc Nephrol。