Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy.
Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy.
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DOI：
10.1111/j.1582-4934.2012.01526.x
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发表时间：
2012-09
影响因子：
5.3
通讯作者：
Watanabe K
中科院分区：
文献类型：
--
作者：
Arumugam S;Thandavarayan RA;Veeraveedu PT;Nakamura T;Arozal W;Sari FR;Giridharan VV;Soetikno V;Palaniyandi SS;Harima M;Suzuki K;Nagata M;Kodama M;Watanabe K
依达拉奉是一种新型的抗氧化剂，它通过捕获羟自由基、淬灭活性氧等作用，对实验性自身免疫性心肌炎（EAM）具有心脏保护作用。然而，依达拉奉是否能预防扩张型心肌病（DCM）的心脏重塑仍有待确定。本研究旨在评估依达拉奉是否减轻心肌纤维化，并检查依达拉奉对DCM大鼠EAM后心功能的影响。免疫后28天，用猪心肌肌球蛋白注射制备大鼠EAM模型，依达拉奉3和10 mg/kg/d腹腔注射，连续28天。将结果与溶剂处理的DCM大鼠进行比较。通过血流动力学和超声心动图研究和组织病理学检查进行心功能检查。Western blotting检测左心室NADPH氧化酶亚基（p47 phox、p67 phox、gp 91 phox和Nox 4）、纤维化标志物（TGF-β1和OPN）、内质网应激标志物（GRP 78和GADD 153）和凋亡标志物（细胞色素C和caspase-3）的表达。依达拉奉治疗的DCM大鼠表现出更好的心脏功能相比，溶剂治疗的大鼠。此外，依达拉奉处理的大鼠左心室NADPH氧化酶亚单位水平的表达显著下调。此外，依达拉奉给药大鼠心肌中的III型胶原阳性细胞数量低于溶剂给药大鼠。我们的研究结果表明，依达拉奉通过调节氧化和ER应激介导的心肌细胞凋亡和纤维化来改善DCM的进展。
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 (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-β1 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.
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影响因子：
5
作者：
Okura, Y;Yamamoto, T;Abo, T
通讯作者：
Abo, T
影响因子：
20.1
作者：
KODAMA, M;HANAWA, H;SHIBATA, A
通讯作者：
SHIBATA, A
影响因子：
3.3
作者：
Shimazaki, Hiroko;Watanabe, Kenichi;Aizawa, Yoshifusa
通讯作者：
Aizawa, Yoshifusa
影响因子：
20.1
作者：
Cesselli, D;Jakoniuk, I;Anversa, P
通讯作者：
Anversa, P
影响因子：
9.2
作者：
Sukumaran V;Watanabe K;Veeraveedu PT;Gurusamy N;Ma M;Thandavarayan RA;Lakshmanan AP;Yamaguchi K;Suzuki K;Kodama M
通讯作者：
Kodama M