Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Arch Med Res. 2011 Apr;42(3):171-81. doi: 10.1016/j.arcmed.2011.04.008.
Patients with diabetes show enhanced susceptibility to myocardial ischemia/reperfusion (MI/R) injury. Epidemiological studies indicated that consumption of α-linolenic acid (ALA) significantly reduces the risk of cardiac events in post-acute myocardial infarction patients. The present study attempted to investigate the effects of ALA intake on MI/R injury in normal and diabetic rats and its mechanisms.
The high-fat diet-fed streptozotocin (HFD-STZ) rat model was developed. Age-matched normal and HFD-STZ rats were randomly assigned to receive normal diet or ALA (oral gavage, 500 μg/kg per day). After 4 weeks of feeding, animals were subjected to 30 min of myocardial ischemia and 4 or 6 h of reperfusion.
Compared with the normal control, HFD-STZ rats showed more severe myocardial functional impairment and injury. Although ALA intake for 4 weeks did not change myocardial function and injury in normal rats, it significantly improved the instantaneous first derivation of left ventricle pressure, reduced infarct size, plasma creatine kinase and lactate dehydrogenase activities, and apotosis at the end of reperfusion in HFD-STZ diabetic rats. Moreover, ALA intake not only significantly reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations but reduced the increase in superoxide production and malonaldialdehyde formation and simultaneously enhanced the antioxidant capacity in the diabetic hearts. Myocardial PI3K expression and Akt phosphorylation were increased by ALA intake in diabetic but not normal rats.
Chronic ALA intake confers cardioprotection in MI/R by exerting anti-inflammatory and anti-oxidative stress effects in diabetic but not normal rats, which is possibly through PI3K-Akt-dependent mechanism.
糖尿病患者对心肌缺血/再灌注(MI/R)损伤的易感性增加。流行病学研究表明,α-亚麻酸(ALA)的消耗显著降低了急性心肌梗死后患者发生心脏事件的风险。本研究试图探讨 ALA 摄入对正常和糖尿病大鼠 MI/R 损伤的影响及其机制。
建立高脂肪饮食喂养链脲佐菌素(HFD-STZ)大鼠模型。将同龄正常和 HFD-STZ 大鼠随机分为正常饮食组或 ALA 组(口服灌胃,每天 500μg/kg)。喂养 4 周后,动物进行 30 分钟心肌缺血和 4 或 6 小时再灌注。
与正常对照组相比,HFD-STZ 大鼠表现出更严重的心肌功能障碍和损伤。尽管 ALA 摄入 4 周并未改变正常大鼠的心肌功能和损伤,但它显著改善了再灌注期末瞬时左心室压力的一阶导数,减少了梗死面积、血浆肌酸激酶和乳酸脱氢酶活性以及凋亡。此外,ALA 摄入不仅显著降低了肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的浓度,而且减少了超氧化物产生和丙二醛形成的增加,同时增强了糖尿病心脏的抗氧化能力。ALA 摄入增加了糖尿病大鼠心肌中 PI3K 的表达和 Akt 的磷酸化,但对正常大鼠没有影响。
慢性 ALA 摄入通过在糖尿病大鼠中发挥抗炎和抗氧化应激作用,对 MI/R 提供心脏保护作用,但在正常大鼠中没有作用,这可能是通过 PI3K-Akt 依赖的机制。