1999 Fiscal Year Final Research Report Summary
Investigation of mechanism of infarct size-reducing effect of α-1,6-glucosidase inhibitor
| Project/Area Number |
10670639
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gifu University |
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Principal Investigator |
MINATOGUCHI Shinya Gifu University, Medicine, Associate Professor, 医学部, 助教授 (20190697)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Hisayoshi Gifu University, Medicine, Professor, 医学部, 教授 (80115930)
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| Project Period (FY) |
1998 – 1999
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| Keywords | α-glucosidases inhibitor / myocardial infarction / stunning / apoptosis / glycogen / lactate |
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| Research Abstract |
1) N-methyl-1-deoxynojirimycin (NMDM) and α-1,6-glucosidase activity, glyconen and lactate
In 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 C
The 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 apoptosis
The 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 stunning
NMDM (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.
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