Li Qianxiao, Yu Qin, Na Rongmei, Liu Baiting
Department of Cardiology, Zhejiang Province Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang 310003, P.R. China.
Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116000, P.R. China.
Exp Ther Med. 2017 Dec;14(6):6152-6158. doi: 10.3892/etm.2017.5338. Epub 2017 Oct 18.
Mice that lacked manganese-superoxide dismutase (Mn-SOD) activity exhibited the typical pathology of dilated cardiomyopathy (DCM). The aim of the present study was to investigate the effect of supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) on heart function and oxidative stress biomarkers in mice with DCM. In the present study, heart/muscle-specific Mn-SOD-deficient mice (H/M-Sod2) were treated with n-3 PUFA (30 mg/kg/day) for 10 weeks, and the reactive oxygen species (ROS) production in their heart mitochondria and cardiac function was subsequently assessed. n-3 PUFA treatment diminished ROS production and suppressed the progression of cardiac dysfunction. Furthermore, n-3 PUFA treatment effectively reversed the cardiac dysfunction and dilatation observed in symptomatic H/M-Sod2 mice. Notably, n-3 PUFA treatment ameliorated a molecular defect in connexin 43. Hematoxylin-eosin staining indicated that the phenotype of DCM was also ameliorated following n-3 PUFA treatment. Furthermore, echocardiography demonstrated that cardiac function was significantly improved in the mice treated with n-3 PUFA (P<0.05). Meanwhile, pre-treatment with n-3 PUFA significantly decreased cardiomyocyte apoptosis (P<0.001). In conclusion, n-3 PUFA treatment is able to prevent murine DCM, primarily by reducing ROS production and improving myocardial apoptosis. Therefore, the impairment of ROS production is proposed as a potential therapy for DCM.
缺乏锰超氧化物歧化酶（Mn-SOD）活性的小鼠表现出扩张型心肌病（DCM）的典型病理特征。本研究的目的是探讨补充ω-3多不饱和脂肪酸（n-3 PUFA）对DCM小鼠心脏功能和氧化应激生物标志物的影响。在本研究中，心脏/肌肉特异性Mn-SOD缺陷小鼠（H/M-Sod2）接受n-3 PUFA（30 mg/kg/天）治疗10周，随后评估其心脏线粒体中的活性氧（ROS）产生和心脏功能。n-3 PUFA治疗减少了ROS产生并抑制了心脏功能障碍的进展。此外，n-3 PUFA治疗有效逆转了有症状的H/M-Sod2小鼠中观察到的心脏功能障碍和扩张。值得注意的是，n-3 PUFA治疗改善了连接蛋白43的分子缺陷。苏木精-伊红染色表明，n-3 PUFA治疗后DCM的表型也得到改善。此外，超声心动图显示，接受n-3 PUFA治疗的小鼠心脏功能显著改善（P<0.05）。同时，n-3 PUFA预处理显著降低了心肌细胞凋亡（P<0.001）。总之，n-3 PUFA治疗能够预防小鼠DCM，主要是通过减少ROS产生和改善心肌细胞凋亡。因此，ROS产生受损被提议作为DCM的一种潜在治疗方法。
