Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
J Cell Mol Med. 2012 Sep;16(9):2176-85. doi: 10.1111/j.1582-4934.2012.01526.x.
Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47(phox), p67(phox), gp91(phox) and Nox4), fibrosis markers (TGF-β(1) and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis.
依达拉奉是一种新型的抗氧化剂，通过捕获羟自由基、淬灭活性氧等方式发挥作用。已有研究报道其对实验性自身免疫性心肌炎（EAM）具有心脏保护作用。然而，依达拉奉是否对扩张型心肌病（DCM）的心肌重构具有保护作用仍有待确定。本研究旨在评估依达拉奉是否能减轻心肌纤维化，并研究依达拉奉对 EAM 后 DCM 大鼠心脏功能的影响。通过在免疫后 28 天给大鼠注射猪心肌肌球蛋白制备 EAM 大鼠模型，我们用 3 和 10mg/kg/天的剂量给大鼠腹腔内注射依达拉奉 28 天。将结果与用载体处理的 DCM 大鼠进行比较。通过血流动力学和超声心动图研究以及组织病理学进行心脏功能检查。通过 Western blot 检测左心室（LV）NADPH 氧化酶亚基（p47(phox)、p67(phox)、gp91(phox)和 Nox4）、纤维化标志物（TGF-β(1)和 OPN）、内质网（ER）应激标志物（GRP78 和 GADD 153）和凋亡标志物（细胞色素 C 和 caspase-3）的 LV 表达。与载体处理的大鼠相比，依达拉奉治疗的 DCM 大鼠的心脏功能更好。此外，依达拉奉治疗的大鼠 LV 中 NADPH 氧化酶亚基水平的表达明显下调。此外，与载体处理的大鼠相比，依达拉奉治疗的大鼠心肌中 III 型胶原蛋白阳性细胞的数量较低。我们的研究结果表明，依达拉奉通过调节氧化应激和 ER 应激介导的心肌凋亡和纤维化来改善 DCM 的进展。
