Docosahexaenoic acid protects against palmitate-induced mitochondrial dysfunction in diabetic cardiomyopathy
Docosahexaenoic acid protects against palmitate-induced mitochondrial dysfunction in diabetic cardiomyopathy
复制标题
二十二碳六烯酸可预防糖尿病心肌病中棕榈酸酯诱导的线粒体功能障碍
DOI：
10.1016/j.biopha.2020.110306
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发表时间：
2020-08-01
影响因子：
7.5
通讯作者：
Gai, Zhibo
中科院分区：
文献类型：
--
作者：
Gui, Ting;Li, Yunlun;Gai, Zhibo
目的：经常食用 n-3 多不饱和脂肪酸与降低心血管发病率和死亡率相关。本研究评估了二十二碳六烯酸 (DHA) 在体外和高脂饮食 (HFD) 喂养的大鼠中对棕榈酸 (PA) 诱导的细胞毒性的治疗作用。方法：将 H9C2 细胞和大鼠原代心肌细胞暴露于 PA 或 PA + DHA 24 小时。通过免疫染色、实时 PCR、心肌细胞收缩和透射电子显微镜评估 PA 诱导的脂毒性和线粒体功能障碍。通过喂养富含 DHA 的参考饮食、HFD 或添加 DHA 的 HFD 的雄性 Sprague-Dawley 大鼠 16 周，评估饮食 DHA 对糖尿病心肌病的影响。通过Masson染色、免疫组织化学和TUNEL检测大鼠心脏组织的氧化应激和脂毒性。结果：体外研究表明膳食DHA可减少心肌病的发生并改善心脏对PA的反应。在大鼠模型中，膳食 DHA 减少了 HFD 诱导的糖尿病心肌病的线粒体氧化应激。结论：膳食 DHA 减少了线粒体氧化应激，并改善了 PA 诱导的脂质毒性。 DHA 摄入量可能通过心肌保护作用对心血管风险产生直接影响。
Objective: Regular consumption of n-3 polyunsaturated fatty acids is associated with decreased cardiovascular morbidity and mortality. This study assessed the therapeutic effect of docosahexaenoic acid (DHA) in palmitic acid (PA)-induced cytotoxicity in vitro and in rats fed a high-fat diet (HFD).Methods: H9C2 cells and rat primary cardiomyoblasts were exposed to PA or PA + DHA for 24 h. PA-induced lipotoxicity and mitochondrial dysfunction were evaluated by immunostaining, real-time PCR, cardiomyocyte contraction and transmission electron microscopy. The effects of dietary DHA on diabetic cardiomyopathy were evaluated in male Sprague-Dawley rats fed a reference diet rich in DHA, an HFD, or an HFD with added DHA for 16 weeks. Oxidative stress and lipotoxicity in rat heart tissue were assayed by Masson staining, immunohistochemistry, and TUNEL.Results: In vitro studies showed that dietary DHA reduced the occurrence of cardiomyopathy and improved cardiac responses to PA. In the rat model, dietary DHA reduced mitochondrial oxidative stress in HFD-induced diabetic cardiomyopathy.Conclusion: Dietary DHA reduced mitochondrial oxidative stress and ameliorated PA-induced lipid toxicity. DHA consumption may have had direct effects on cardiovascular risk via myocardial protection.