Ramezani-Aliakbari Fatemeh, Badavi Mohammad, Dianat Mahin, Mard Seyyed Ali, Ahangarpour Akram
Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Iran J Pharm Res. 2020 Summer;19(3):248-257. doi: 10.22037/ijpr.2020.1101144.
Trimetazidine (TMZ) improves endothelial dysfunction. However, its beneficial effect on endothelial miRNAs is unexplored in diabetes. The aim of the present study was to evaluate the effects of TMZ on plasma miRNA-24 and miRNA-126, dyslipidemia, inflammation, and blood pressure in the diabetic rats. Adult male Sprague-Dawley rats were randomly assigned into four groups (250 ± 20 g, n = 8): a control (C), an untreated diabetic (D), a diabetic group administrated with TMZ at 10 mg/kg (T10), and a diabetic group administrated with TMZ at 30 mg/kg (T30) for eight weeks. Diabetes was induced by injection of alloxan (120 mg/kg). The plasma levels of miR-24, miR-126, lipid profile, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), blood glucose, body weight and systolic blood pressure were measured. The diabetic rats showed decreased plasma miR-24, HDL-c ( < 0.05), miR-126 ( < 0.01), body weight changes percent, body weight, and systolic blood pressure ( < 0.001) and increased triglycerides (TG), VLDL-c ( < 0.05), TNF-α, total cholesterol (TC) ( < 0.01) glucose, MDA and IL-6 ( < 0.001). Interestingly, all these changes were significantly improved by TMZ treatment. Our findings propose that TMZ has protective effects on decreased plasma miR-24 and miR-126 levels, inflammation, dyslipidemia and hypotension, and it may participate in endothelial dysfunction and atherosclerosis.
曲美他嗪(TMZ)可改善内皮功能障碍。然而,其对糖尿病患者内皮微小RNA(miRNA)的有益作用尚未得到研究。本研究的目的是评估TMZ对糖尿病大鼠血浆miRNA - 24和miRNA - 126、血脂异常、炎症和血压的影响。成年雄性Sprague - Dawley大鼠随机分为四组(体重250±20 g,n = 8):对照组(C)、未治疗的糖尿病组(D)、接受10 mg/kg TMZ治疗的糖尿病组(T10)和接受30 mg/kg TMZ治疗的糖尿病组(T30),持续治疗八周。通过注射四氧嘧啶(120 mg/kg)诱导糖尿病。测量血浆中miR - 24、miR - 126、血脂谱、丙二醛(MDA)、肿瘤坏死因子 - α(TNF - α)和白细胞介素 - 6(IL - 6)、血糖、体重和收缩压。糖尿病大鼠血浆miR - 24、高密度脂蛋白胆固醇(HDL - c)(<0.05)、miR - 126(<0.01)、体重变化百分比、体重和收缩压(<0.001)降低,甘油三酯(TG)、极低密度脂蛋白胆固醇(VLDL - c)(<0.05)、TNF - α、总胆固醇(TC)(<0.01)、血糖、MDA和IL - 6(<0.001)升高。有趣的是,TMZ治疗可显著改善所有这些变化。我们的研究结果表明,TMZ对血浆miR - 24和miR - 126水平降低、炎症、血脂异常和低血压具有保护作用,并且可能参与内皮功能障碍和动脉粥样硬化。