Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Bioimpacts. 2015;5(1):3-8. doi: 10.15171/bi.2015.02. Epub 2015 Feb 21.
Acute treatment with metformin has a cardio-protective effects by suppression of inflammatory responses during myocardial infarction (MI) through activation of AMP-activated protein kinase (AMPK). Neutrophils have a pivotal role during MI-induced inflammatory responses. Some anti-inflammatory treatments have decreased cardiac injury and infarct size in MI. Here we evaluated the effects of chronic pre-treatment with metformin on myocardial remodeling and neutrophil recruitment after isoproterenol-induced MI.
Male wistar rats were randomly assigned into 6 groups (n=6) of untreated control, sham, isoproterenol (Iso), and pre-treated orally with 25, 50, and 100 mg/kg of metformin, twice daily, for 14 days. Isoproterenol was injected subcutaneously (sc) at 13th and 14th days for induction of acute MI. Histopathological examinations were done on the harvested hearts. Number of neutrophils in peripheral blood and their infiltration to myocardium were evaluated by Gimsa staining and myeloperoxidase (MPO) assay, respectively.
Histopathological analysis showed a significant attenuation of isoproterenol-induced cardiomyocyte necrosis and fibrosis by all three doses of metformin. The heart to body weight ratio was also decreased with all doses of metformin. Pre-treatment with metformin in comparison to Iso (MI) group reduced peripheral neutrophils (p<0.05, p<0.01, and p<0.001 at 25, 50, and 100 mg/kg; respectively) as well as MPO activity (p<0.05 and p<0.01 at 50 and 100 mg/ kg, respectively).
Pre-treatment with metformin decreased post-MI myocardial injuries by reducing cardiac remodeling and myocardial neutrophil activity. The results could be explained as a new mechanism for cardio-protective effect of metformin.
在心肌梗死（MI）期间，通过激活 AMP 激活蛋白激酶（AMPK）抑制炎症反应，二甲双胍的急性治疗具有心脏保护作用。中性粒细胞在 MI 诱导的炎症反应中起着关键作用。一些抗炎治疗已减少了 MI 中的心脏损伤和梗塞面积。在这里，我们评估了慢性预用二甲双胍对异丙肾上腺素诱导的 MI 后心肌重构和中性粒细胞募集的影响。
雄性 wistar 大鼠被随机分为 6 组（n=6）：未处理的对照组、假手术组、异丙肾上腺素（Iso）组和预用 25、50 和 100mg/kg 的二甲双胍口服治疗，每天两次，共 14 天。异丙肾上腺素于第 13 天和第 14 天皮下（sc）注射以诱导急性 MI。对收获的心脏进行组织病理学检查。通过 Gimsa 染色和髓过氧化物酶（MPO）测定分别评估外周血中性粒细胞数量及其向心肌的浸润。
组织病理学分析表明，所有三种剂量的二甲双胍均可显著减轻异丙肾上腺素诱导的心肌细胞坏死和纤维化。二甲双胍还降低了心脏与体重的比值。与 Iso（MI）组相比，二甲双胍预处理可减少外周血中性粒细胞（p<0.05，p<0.01 和 p<0.001 分别为 25、50 和 100mg/kg；分别）和 MPO 活性（p<0.05 和 p<0.01 分别为 50 和 100mg/kg）。
预用二甲双胍可通过减少心肌重塑和心肌中性粒细胞活性来减少 MI 后的心肌损伤。结果可以解释为二甲双胍心脏保护作用的新机制。
