Hayashi M, Nasa Y, Tanonaka K, Sasaki H, Miyake R, Hayashi J, Takeo S
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
J Mol Cell Cardiol. 1995 Sep;27(9):2031-41. doi: 10.1016/0022-2828(95)90024-1.
N-3 polyunsaturated fatty acids have been epidemiologically demonstrated to decrease the incidence of ischaemic heart disease. The present study was undertaken to examine the effects of long-term treatment with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on hypoxia/reoxygenation injury of isolated adult rat cardiomyocytes. Rats, fed with standard rat chow, were treated with 100 to 1000 mg/kg/day EPA or 1000 mg/kg/day DHA for 4 weeks and their cardiomyocytes were isolated by collagenase treatment. The cardiomyocytes, approximately 90% of which were rod-shaped, were subjected to 150-min hypoxia/15-min reoxygenation, and their survivals at the ends of hypoxia and reoxygenation were determined. Treatment with either 1000 mg/kg/day of EPA or DHA resulted in a significant increase in the survival of the cardiomyocytes (39.9 +/- 1.1 and 38.3 +/- 3.0%, n = 14 and 8, respectively v 26.7 +/- 1.6%, n = 8, for untreated group). Treatment with EPA increased eicosapentaenoic (377% increase), oleic (25% increase) and linoleic acid (37% increase) contents in the myocardial total phospholipids without changes in the total phospholipid content, whereas treatment with DHA did not increase DHA incorporation into the myocardial phospholipids. The results suggest that EPA and DHA protect the myocardial cells against hypoxia-reoxygenation-induced injury. Although alterations in myocardial phospholipid composition were observed by treatment with EPA or DHA, the primary mechanism underlying the benefit of EPA or DHA intake is unlikely to be related to increased incorporation of their own fatty acids into the myocardial phospholipids, or the mechanism may be different in each n-3 unsaturated fatty acid employed.
流行病学研究已证实，N-3多不饱和脂肪酸可降低缺血性心脏病的发病率。本研究旨在探讨长期服用二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）对成年大鼠离体心肌细胞缺氧/复氧损伤的影响。给喂食标准大鼠饲料的大鼠每日按100至1000 mg/kg的剂量投喂EPA或按1000 mg/kg的剂量投喂DHA，持续4周，然后通过胶原酶处理分离出它们的心肌细胞。这些心肌细胞约90%呈杆状，经历150分钟的缺氧/15分钟的复氧过程，并测定其在缺氧和复氧结束时的存活率。每日按1000 mg/kg的剂量投喂EPA或DHA均可显著提高心肌细胞的存活率（分别为39.9±1.1%和38.3±3.0%，n分别为14和8；未处理组为26.7±1.6%，n = 8）。投喂EPA可使心肌总磷脂中的二十碳五烯酸含量增加377%、油酸含量增加25%、亚油酸含量增加37%，而总磷脂含量不变；而投喂DHA并未使DHA掺入心肌磷脂中。结果表明，EPA和DHA可保护心肌细胞免受缺氧-复氧诱导的损伤。尽管投喂EPA或DHA可观察到心肌磷脂组成的改变，但摄入EPA或DHA有益的主要机制不太可能与其自身脂肪酸更多地掺入心肌磷脂有关，或者每种所使用的n-3不饱和脂肪酸的机制可能不同。
