A novel anti‐diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits
A novel anti‐diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits
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一种新型抗糖尿病药物米格列醇可显着减少兔子心肌梗塞的面积
DOI：
10.1038/sj.bjp.0702970
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发表时间：
1999
影响因子：
7.3
通讯作者：
H. Fujiwara
中科院分区：
文献类型：
--
作者：
S. Minatoguchi;M. Arai;Y. Uno;T. Kariya;Y. Nishida;K. Hashimoto;M. Kawasaki;G. Takemura;T. Fujiwara;H. Fujiwara
本文研究了人类抗糖尿病新药N-羟乙基-1-脱氧野生霉素(米格列醇)是否能抑制α-1，6-葡萄糖苷酶糖原脱支酶，降低糖原分解速率，抑制α-1，4-葡萄糖苷酶，从而缩小兔心肌梗死范围。兔冠状动脉结扎30min，再灌流48h。与生理盐水对照组(41.7±2.3%，n=10)相比，缺血前给予1 mg kg−-1米格列醇(42.7±4.0%，n=10)并不能减少梗塞面积(占危险区域的百分比)。而缺血前给予米格列醇5或10 kg−1(25.7±4.5%，n=10和14.6±2.4%，n=10)均可显著降低上述指标，且呈剂量依赖性，且不影响血压、心率和血糖水平。再灌流前给予米格列醇10 mg kg−1(35.0±3.0%，n=10)，未见明显缩小心肌梗死面积的作用。另40只兔在缺血前给予1，5和10 mg kg−1米格列醇或生理盐水，每组10只，分别于缺血30 时处死动物进行生化分析。米格列醇在缺血30 时显著保存糖原含量，显著抑制缺血区乳酸蓄积，且呈剂量依赖关系。使用米格列醇的缺血前治疗，而不是再灌流前治疗，显著减少心肌梗死范围，与血压和心率无关。米格列醇对心肌梗死面积、糖原分解和乳酸形成的影响呈剂量依赖性，提示其作用机制可能与抑制糖原分解有关。因此，米格列醇可能对冠心病和糖尿病都有好处。
We examined whether N‐hydroxyethyl‐1‐deoxynojirimycin (miglitol), a new human anti‐diabetic drug with effects to inhibit α‐1,6‐glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit α‐1,4‐glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30‐min coronary occlusion followed by 48‐h reperfusion. The infarct size as a percentage of area at risk was not reduced by pre‐ischaemic treatment with 1 mg kg−1 miglitol (42.7±4.0%, n=10) compared with the saline control group (41.7±2.3%, n=10). However, it was significantly and dose‐dependently reduced by pre‐ischaemic treatment with 5 or 10 mg kg−1 of miglitol (25.7±4.5%, n=10, and 14.6±2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct‐size reducing effect after pre‐reperfusion treatment with 10 mg kg−1 of miglitol (35.0±3.0%, n=10). Another 40 rabbits given 1, 5 and 10 mg kg−1 of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. Pre‐ischaemic treatment, but not pre‐reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose‐dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.
影响因子：
20.1
作者：
MURRY, CE;RICHARD, VJ;JENNINGS, RB
通讯作者：
JENNINGS, RB