RESEACH FOR THE PATHOGENESIS OF DIABETIC RETINOPATHY

糖尿病视网膜病变发病机制的研究

• 批准号: 12671106
• 负责人: HAMADA Yoji
• 金额: $ 2.37万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671106/
• 关键词: Diabetic Complications; Retinal MicrovascuLar Pericytes; Apoptosis; Poiyol Pahtway; Protein Kinase C; Oxidentive Stress; Aldose Reductase Inhibitior; プロティンキナーゼC

The mechanisms of the glucose-induced apoptosis in retinal pericytes were investigated to evaluate the pathogenesis of diabetic retinopathy. Under the 20 mM glucose condition, intracellular calcium concentrations and caspase-3 activities were significantly increased, and reduced glutathione contents and PKC activities were significantly decreased, compared with those under the 5. 5 mM glucose condition. These abnormalities were all significantly prevented by an aldose reductase inhibitor, SNK-860. Glucose-induced apoptosis was partially but significantly prevented by SNK-860, a calpain inhibitor, or reduced glutathione supplementation, and completely normalized by a caspase-3 inhibitor. These observations suggest that glucose-induced apoptosis in retinal pericytes would be mediated through an aldose reductase sensitive pathway including caicium-calpain cascade, increased oxidative stress and decreased PKC activities, and that caspase-3 would be located furthest down stream of these apoptotic signals.

探讨葡萄糖诱导视网膜周细胞凋亡的机制，以探讨糖尿病视网膜病变的发病机制。20 mM葡萄糖条件下，细胞内钙离子浓度和caspase-3活性显著升高，还原型谷胱甘肽含量和PKC活性显著降低。5 mM葡萄糖条件。这些异常均被醛糖还原酶抑制剂SNK-860显著预防。SNK-860（钙蛋白酶抑制剂）或还原型谷胱甘肽补充剂可部分但显著地预防葡萄糖诱导的细胞凋亡，并通过caspase-3抑制剂完全正常化。这些观察结果表明，葡萄糖诱导的视网膜周细胞凋亡将通过包括钙-钙蛋白酶级联反应、氧化应激增加和PKC活性降低的醛糖还原酶敏感途径介导，并且caspase-3将位于这些凋亡信号的最下游。

项目成果

Nakamura J.: "Glucose-induced hyperproliteration of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity"Diabetologia. 44. 480-487 (2001)

Nakamura J.：“通过多元醇途径过度活跃，葡萄糖诱导培养的大鼠主动脉平滑肌细胞过度增殖”Diabetologia。

Yasuda Y: "Role of PKC and TGF-β receptor in glucose-induced proliferation of smooth muscle cells"Biochem Biophys Res Commun. 281. 71-77 (2001)

安田 Y：“PKC 和 TGF-β 受体在葡萄糖诱导的平滑肌细胞增殖中的作用”Biochem Biophys Res Commun. 281. 71-77 (2001)。

Keiko Naruse: "Aldose Reductase Inhibition Prevents Glucose-induced Apoptosis in cultured Bovine Retinal Microvascular Pericytes"Exp.Eye.Res.. 71. 309-315 (2000)

Keiko Naruse：“醛糖还原酶抑制可防止培养的牛视网膜微血管周细胞中葡萄糖诱导的细胞凋亡”Exp.Eye.Res.. 71. 309-315 (2000)

Naruse K: "Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes"Exp Eye Res. 71. 309-315 (2000)

Naruse K：“醛糖还原酶抑制可防止培养的牛视网膜微血管周细胞中葡萄糖诱导的细胞凋亡”Exp Eye Res。

Nakamura J: "Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity"Diabetologia. 44. 480-487 (2001)

Nakamura J：“通过多元醇途径过度活跃，葡萄糖诱导培养的大鼠主动脉平滑肌细胞过度增殖”Diabetologia。