Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Egypt.
J Pharm Pharmacol. 2018 Nov;70(11):1521-1530. doi: 10.1111/jphp.13000. Epub 2018 Sep 2.
To investigate the effect of dimethyl fumarate (DMF) on Toll-like receptor (TLR) signalling pathway in isoproterenol (ISO)-induced cardiac hypertrophy in rats.
Sixty adult male Sprague-Dawley rats were randomly allocated into three groups. group I: rats received the vehicles only; group II: rats were treated with ISO (5 mg/kg per day S.C.) to induce cardiac hypertrophy for 7 days; and group III: rats were given DMF (25 mg/kg per 12 h P.O.) for 28 days, and at the last 7 days, they were treated with ISO (5 mg/kg per day S.C.).
Pretreatment with DMF decreased heart-to-body weight ratio, heart rate and blood pressure and improved the electrocardiographic patterns when compared with ISO group. DMF exhibited cardioprotective effect as evidenced by the reduction in cardiac troponin I, creatine kinase-MB and atrial natriuretic peptide levels. Moreover, DMF alleviated the changed oxidative stress and inflammatory biochemical markers through its anti-inflammatory and antioxidant effects. DMF interfered with TLR signalling pathway, evidenced by decreased levels of the TLR adaptor protein MyD88 and p-ERK1/2 and increased p-Akt level.
Dimethyl fumarate exerted cardioprotective effect against ISO-induced cardiac hypertrophy. This effect is suggested to be through interfering with TLR signalling pathway.
研究富马酸二甲酯（DMF）对异丙肾上腺素（ISO）诱导的大鼠心肌肥厚中 Toll 样受体（TLR）信号通路的影响。
将 60 只成年雄性 Sprague-Dawley 大鼠随机分为 3 组。组 I：大鼠仅接受载体；组 II：大鼠接受 ISO（5mg/kg/d，皮下注射）以诱导心肌肥厚 7 天；组 III：大鼠给予 DMF（25mg/kg/12h，口服）28 天，在最后 7 天，他们接受 ISO（5mg/kg/d，皮下注射）。
与 ISO 组相比，DMF 预处理降低了心脏重量与体重比、心率和血压，并改善了心电图模式。DMF 通过降低心肌肌钙蛋白 I、肌酸激酶-MB 和心房利钠肽水平表现出心脏保护作用。此外，DMF 通过其抗炎和抗氧化作用减轻了氧化应激和炎症生化标志物的变化。DMF 通过降低 TLR 衔接蛋白 MyD88 和 p-ERK1/2 的水平以及增加 p-Akt 水平来干扰 TLR 信号通路。
富马酸二甲酯对 ISO 诱导的心肌肥厚具有心脏保护作用。这种作用可能是通过干扰 TLR 信号通路实现的。
