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

1)N-甲基-1-脱氧野生霉素和α-1，6-葡萄糖苷酶活性、糖原和乳酸在体外兔心脏实验中，N-甲基-1-脱氧野生霉素对α-1，6-葡萄糖苷酶活性的抑制作用呈剂量依赖性。在活体动物模型中，NMDM(100 mg/kg)静脉注射。抑制缺血时α-1，6-葡萄糖苷酶活性而不影响磷酸酶活性，抑制心肌糖原分解和乳酸蓄积。蛋白激酶C抑制剂星形孢子素(50μg/kg，i.v)可完全阻断上述作用。3)NMDM与细胞凋亡：缺血30min再灌流4h后，NMDM组心肌梗死区TUNEL阳性细胞百分率(3.8±1.5%)明显低于对照组(10.7±1.9%)。显著改善兔心肌缺血10min再灌流模型的局部心肌收缩功能。这表明，NMDM的效果令人惊叹。

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.