Investigation of mechanism of infarct size-reducing effect of α-1,6-glucosidase inhibitor

α-1,6-葡萄糖苷酶抑制剂减少梗塞面积作用机制的研究

• 批准号: 10670639
• 负责人: MINATOGUCHI Shinya
• 金额: $ 2.05万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670639/
• 关键词: α-glucosidases inhibitor; myocardial infarction; stunning; apoptosis; glycogen; lactate; α-グルマシダーゼ阻害薬; グリマーゲン; α-1,6-glucosidase; protein kinase C; glycogen; N-methyl-1-deoxynojirimycirn; lactate

1) N-methyl-1-deoxynojirimycin (NMDM) and α-1,6-glucosidase activity, glyconen and lactateIn an in vitro study of rabbit heart, NMDM inhibited the α-1,6-glucosidase activity in a dose dependent manner. In an in vivo rabbit model, NMDM (100mg/kg, i.v.) inhibited the α-1,6-glucosidase activity without affecting phosphorylase activity during ischemia, and inhibited the breakdown myocardial glycogen and the lactate accumulation.2) NMDM and protein kinase CThe infarct size-reducing effect of NMDM (100 mg/kg, i.v.) was complelely blocked by pretreatment with protein kinase C inhibitor staurosporine (50 μg/kg i.v.). Translocation of the PKC-ε, one of the subtypes of protein kinase C, by NMDM was observed during ischemia by western blotting method.3) NMDM and apoptosisThe percentage of TUNEL-positive myocytes in the infarcted area of the rabbits with 30 min ischemia and 4 hour reperfusion was significantly reduced in the NMDM group (3.8±1.5 %) as compared with control group (10.7±1.9 %).4) NMDM and stunningNMDM (100 mg/kg, i.v.) significantly improved the regional myocardial contractile function in a 10 min-ischemia and reperfusion model of rabbits. This suggests that NMDM improves stunning.

1)N-甲基-1-脱氧野尻霉素（NMDM）与α-1，6-葡萄糖苷酶活性、葡萄糖苷和乳酸盐在离体兔心脏研究中，NMDM以剂量依赖性方式抑制α-1，6-葡萄糖苷酶活性。在体内兔模型中，NMDM（100 mg/kg，i. v.）NMDM（100 mg/kg，i. v.）和蛋白激酶C（PKC）的作用：NMDM（100 mg/kg，i. v.）用蛋白激酶C抑制剂staurosporine（50 μg/kg）预处理可完全阻断上述作用。蛋白激酶C亚型之一的PKC-ε易位，NMDM组缺血30 min再灌注4 h梗死区心肌细胞TUNEL阳性细胞百分率明显低于对照组（P < 0. 05），缺血30 min再灌注4 h梗死区心肌细胞TUNEL阳性细胞百分率明显低于对照组（P < 0. 05（3.8± 1.5%）与对照组（10.7± 1.9%）比较。显著改善缺血再灌注10 min家兔局部心肌收缩功能。这表明NMDM改善了击晕。

项目成果

Masazumi Arai, Shinya Minatoguchi, et al: "N-Methyl-1-Deoxynojirimycin(MCR-14), an α-Glycosidase inhibitor, Markedly Reduced Infant Size in Rabbit Hearts"Circulation. 97. 1290-1297 (1998)

Masazumi Arai、Shinya Minatoguchi 等人：“N-甲基-1-脱氧野尻霉素 (MCR-14)，一种 α-糖苷酶抑制剂，可显着减小兔心脏中的婴儿大小”循环。

Arai M, et al.: "N-Methyl-1-Deoxynojirimycin (MOR-14), an α-Glucosidase Inhibitor, Markedly Reduced Infarct Size in Rabbit Hearts"Circulation. 97. 1290-1297 (1998)

Arai M 等人：“N-甲基-1-脱氧野尻霉素 (MOR-14)，一种 α-葡萄糖苷酶抑制剂，可显着减少兔心脏中的梗塞面积”循环。 97. 1290-1297 (1998)

Masazumi Arai,Shinya Minatoguchi et al.: "N-methyl-1-Deoxynojirimycin(MOR-14),in α-Glucosidase inhibitor,Markedly Reduced Infant Size in Rabbit Hearts"Circulation. 97. 1290-1297 (1998)

Masazumi Arai、Shinya Minatoguchi 等人：“N-甲基-1-脱氧野尻霉素 (MOR-14)，在 α-葡萄糖苷酶抑制剂中，兔心脏中的婴儿尺寸显着减小”循环。

M.Arai, S Minatoguchi: "N-Methyl-1-Deaxynojirimycin (MOR-14), an α Gluresidase Inhibitor, Markedly Reduced the lufarct Size in Rabbit Hearts." Circulation. 97. 1290-1297 (1998)

M.Arai, S Minatoguchi：“N-甲基-1-Deaxynojirimycin (MOR-14)，一种 α 葡萄糖苷酶抑制剂，显着减小了兔心脏中的肺动脉大小。97. 1290-1297 (1998)。