曲美他嗪对糖尿病大鼠缺血-再灌注心律失常的影响
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The Beneficial Effects of Trimetazidine on Reperfusion–Induced Arrhythmia in Diabetic Rats
背景与目的：曲美他嗪（TMZ）是一类抗心肌缺血药物，其对糖尿病心肌等并发症中具良好治疗效果。本研究旨在探讨TMZ对糖尿病大鼠缺血-再灌注心律失常的影响。
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方法：SD大鼠250 ± 20 g，共32只，随机分为四组：对照组（C）、糖尿病组（D）、TMZ低剂量组（10 mg/kg, D+T10）、TMZ高剂量组（30 mg/kg, D+T30）；TMZ连续8天灌胃，每天一次；单次注射四氧嘧啶120 mg/kg建立糖尿病大鼠模型；缺血30min再灌注120min，记录心律失常类型及评分、左室功能、心肌梗死面积、LDH、CK-MB、cTnI,使用单因素方差分析、LSD检验、Fisher精确概率法统计数据。
结果：与C组相比，D组心律失常持续时间延长、心律失常评分明显增高(p < 0.001)，心肌梗死面积(p < 0.001)、心肌收缩功能( ± dp/dt)、LDH、CK-MB、cTnI明显下降(p < 0.05)；与D组比较，TMZ组心律失常持续时间明显缩短(p < 0.001)，心律失常评分明显降低、± dp/dt、LDH,、CK-MB, cTnI明显减少 (p < 0.05)，心肌梗死面积减小(p < 0.01)。
结论：TMZ可明显降低糖尿病鼠缺血-再灌注心律失常的发生风险。
Ramezani-Aliakbari F, Badavi M, Dianat M, et al. The Beneficial Effects of Trimetazidine on Reperfusion-Induced Arrhythmia in Diabetic Rats[J]. Experimental and Clinical Endocrinology & Diabetes, 2018.
BACKGROUND:Trimetazidine (TMZ), as an anti-ischemic drug, plays a critical role in protecting against cardiovascular complications induced by diabetes. This study was therefore aimed to evaluate the protective effects of TMZ on reperfusion-induced arrhythmias in the diabetic rats.
METHODS:Male Sprague-Dawley rats (250 ± 20 g) were randomly assigned to four (n = 8): control rats (C), alloxan induced diabetic rats (D), diabetic rats treated with TMZ (10 mg/kg, D + T10), diabetic rats treated with TMZ (30 mg/kg, D + T30).TMZ was treated orally once daily for 8 weeks. Diabetes was induced by a single intraperitoneal injection of alloxan (120 mg/kg). Ischemia-reperfusion (I/R) was carried out via 30 min of ischemia and following120-min reperfusion. The magnitude and score of arrhythmia, the left ventricular function, infarct size, lactate dehydrogenase (LDH), myocardial creatine kinase (CK-MB) and troponin (cTnI) were measured. The findings were evaluated by two-way repeated measures and one-way ANOVA followed by LSD post hoc test and Fisher's exact test for incidence percentage.
RESULTS:The duration, incidence and score of arrhythmia (p < 0.001), infarct size (p < 0.01) were significantly increased, the cardiac contractility ( ± dp/dt), LDH, CK-MB (p < 0.001) and cTnI (p < 0.05) were significantly decreased in the diabetic rats in comparison with the control group. However, treatment with TMZ in the diabetic rats was significantly improved the duration (p < 0.001), incidence and score of arrhythmia, ± dp/dt LDH, CK-MB, cTnI (p < 0.05) and infarct size (p < 0.01) in comparison with the untreated diabetic group.
CONCLUSIONS:The present study indicates anti-arrhythmic effect of TMZ in reducing arrhythmias induced by reperfusion in the diabetic rats.
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