ω-3多不饱和脂肪酸对糖尿病心血管的保护作用

ω—3多不饱和脂肪酸（ω-3 polyunsaturated fatty acids,ω-3 PUFA）是细胞膜磷脂的重要组成部分,参与调节膜介导的胰岛素信号转导、脂肪酶生物活性的发挥、类二十烷酸物质合成等多种生物活动,并参与调控糖脂代谢的基因表达,是人体必需的脂肪酸。其中以二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）研究最为深入。大量流行病学及临床试验显示ω-3 PUFA具有心血管保护作用。美国心脏协会推荐心血管病患者食用深海鱼或鱼油胶囊以添加ω-3 PUFA（1g／d）,降低心血管事件的发生率。     

ω-3多不饱和脂肪酸防治心血管疾病的研究进展

ω-3多不饱和脂肪酸是人体必需的营养物质,具有降低甘油三酯、抑制动脉粥样硬化斑块破裂、抑制血小板聚集、抗炎、抗氧化等多种作用。关于补充ω-3多不饱和脂肪酸是否能够有效降低心血管疾病的发生风险,目前尚无定论。近年来新的随机对照研究及Meta分析结果肯定了ω-3多不饱和脂肪酸尤其是二十碳五烯酸（EPA）在特定人群中的心血管保护作用,更多的指南开始重视ω-3多不饱和脂肪酸的临床应用。本文就近年来ω-3多不饱和脂肪酸在心血管疾病防治领域的临床研究进展进行综述。     

ω-3多不饱和脂肪酸对心肌离子通道的影响

动物实验及大规模临床试验表明ω-3多不饱和脂肪酸具有预防致死性心律失常作用,但其抗心律失常机制尚不清楚。多数研究认为ω-3多不饱和脂肪酸影响心肌细胞上的离子通道的活动,尤其是电压依赖性的钠通道、钾通道和钙通道,可能是其抗心律失常作用的机制。     

重视ω-3多不饱和脂肪酸在危重患者的应用

营养支持是危重患者必不可少的治疗手段,随着重症医学的发展与完善,营养支持治疗也随之在不断的更新与进步中.从早期简单的营养物质补充到拥有多种营养底物,多条营养途径,可根据患者不同情况建立个体化的营养方案,再到目前非常热点的药理学营养(nutritional pharmacology)或免疫营养(immunonutrition).     

不同比例ω-3/ω-6多不饱和脂肪酸对DSS诱导大鼠急性结肠炎的影响

目的:探讨不同比例ω-3/ω-6多不饱和脂肪酸对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导大鼠急性结肠炎影响及其可能的作用机制.方法:32只1月龄♂SD大鼠随机分为4组,每组8只,A:普通饲料对照组,B:ω-3/ω-6PUFA 1∶1组、C:ω-3/ω-6 PUFA 1∶3组,D:ω-3/ω-6 PUFA 1∶30组.4组大鼠不同饲料喂养6 wk;随后B、C、D组大鼠自由饮用3%DSS溶液7 d,诱发急性结肠炎模型;A组大鼠自由引用普通水7 d.比较各组大鼠结肠炎症状评分、病理炎症评分和结肠组织前列腺素E2(prostaglandin E2,PGE2)、核因子-kB(nuclear factor-kB,NF-kB)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、血清白介素-6(interleukin-6,IL-6)的含量.结果:B组大鼠结肠炎症程度积分显著低于C、D组,分别为2.8±1.2、4.3±1.1、5.6±1.3(P<0.05,P<0.01).B组大鼠结肠炎病理学评分显著低于C、D组,分别为3.2±2.0、35.0±28.8、27.0±25.8(P<0.01,P<0.01).B、C组大鼠结肠组织中PGE2含量低于D组,分别为443.4ng/100g组织±67.3 ng/100g组织、419.5ng/100g组织±52.6 ng/100 g组织、541.2±68.5(ng/100 g组织)(P<0.05,P<0.01).B、C组大鼠结肠组织中TNF-α含量低于D组,分别为189.2 ng/100g组织±27.0 ng/100 g组织、173.2 n g/100g组织±50.2 n g/100 g组织、270.3 ng/100g组织±49.1 ng/100 g组织(P<0.01,P<0.01).B组大鼠血清中IL-6含量低于C、D组,分别为97.1 ng/L±8.2 ng/L、129.1 ng/L±5.5 ng/L、125.4 ng/L±19.6 ng/L(P<0.01,P<0.05).B、C、D大鼠结肠组织中NF-kB含量分别为497.9 ng/100g组织±50.7 ng/100 g组织、569.1 ng/100g组织±121.2 ng/100 g组织、582.5 ng/100g组织±123.1 ng/100 g组织,无统计学差异.结论:提高以ω-3/ω-6 PUFA的比例对于DSS诱导的大鼠急性结肠炎症具有保护作用,尤其是当ω-3/ω-6 PUFA比例提高到1∶1保护作用最明显.随着ω-3 PUFA的比例升高,ω-3/ω-6PUFA1∶1组较ω-3/ω-6 PUFA1:30组大鼠的炎症评分、病理评分以及相关的炎症因子如PGE2、TNF-α、IL-6都有所下降.向饮食中添加适量ω-6 PUFA或可成为治疗炎症性肠病新方向.     

ω-3多不饱和脂肪酸在体外胰腺腺泡细胞培养体系中的炎症调控作用及机制

目的 探讨ω-3多不饱和脂肪酸(ω-3 PUFAs)对急性胰腺炎早期炎症反应的作用.方法 培养胰腺腺泡细胞系AR42J,随机分为A组(空白对照)、B组(ω-3 PUFAs预处理后蛙皮素刺激)、C组(仅用蛙皮素刺激);实时荧光定量PCR检测各组细胞肿瘤坏死因子(TNF)α、白细胞介素(IL) -6和线粒体解偶联蛋白-2(UCP-2)mRNA表达;Western Blot检测细胞核中NF-κB p65亚单位的含量;Hoeehst33342/PI染色检测细胞坏死.结果 B组TNFα、IL -6、UCP-2 mRNA表达水平、细胞核NF - κBp 65含量及细胞坏死率与C组相比均明显减少,差异有统计学意义[(0.69±0.10)vs(1.34±0.19),P＜0.001;(0.69±0.06) vs( 1.39±0.06),P＜0.001;(0.58±0.12)vs(1.26±0.07),P＜0.001;(0.54±0.09) vs (0.92±0.09),P＜0.001;(0.20±0.01)vs(0.35±0.03),P＜0.001;F =62.718～157.426,P均＜0.05].而B组、C组TNFα、IL -6、UCP-2 mRNA表达水平、细胞核NF-κBp65亚单位含量及细胞坏死率均高于A组,差异有统计学意义[(0.69±0.10)、(1.34±0.19) vs (0.34±0.05),P=0.003、P＜0.001;(0.69±0.06)、(1.39±0.06) vs (0.23±0.03),P=0.001、P＜0.001; (0.58±0.12)、(1.26±0.07)vs(0.32±0.08),P=0.003、P＜0.001; (0.54 +0.09)、(0.92±0.09)vs(0.26±0.12),P＜0.001、P＜0.001; (0.20±0.01)、(0.35±0.03) vs (0.13±0.03),P=0.024、P＜0.001;F=62.718～157.426,P均＜0.05].结论 ω-3 PUFAs可能抑制急性胰腺炎早期炎症反应.     

ω-3多不饱和脂肪酸的结构、代谢及与动脉粥样硬化的关系

ω-3多不饱和脂肪酸可以通过调节血脂谱、改善内皮功能、抗炎、稳定斑块等多种机制发挥抗动脉粥样硬化作用。本研究综述了ω-3多不饱和脂肪酸的结构、代谢及抗动脉粥样硬化可能的机制和进展。     

ω-3多不饱和脂肪酸胶丸对非酒精性脂肪肝患者的治疗作用

目的:探讨ω-3多不饱和脂肪酸胶丸(海狗油)治疗非酒精性脂肪肝(单纯性脂肪肝及非酒精性脂肪性肝炎)的治疗效果及临床有效剂量.方法:单纯性脂肪肝或非酒精性脂肪性肝炎患者46例.随机分为3组:ω-3多不饱和脂肪酸胶丸低剂量组(每天8粒,n=15)、高剂量组(每天10粒,n=15)和安慰剂组(n=16),进入双盲期,疗程24 wk.观察患者治疗前,治疗后12、24 wk的肝功能、血脂及B超评分.结果:低剂量和高剂量组患者治疗12、24 wk后,B超评分均有所改善,与治疗前比较差异有统计学意义(9.07±3.20,8.00±2.42 vs 11.20±3.00;8.33±2.44,7.07±2.52 vs 10.40±2.06,均P<0.01),而安慰剂组用药前后比较差异无统计学意义.高剂量组用药24 wk后血清甘油三脂水平出现明显下降,且与治疗前比较差异有统计学意义(1.68±0.77 mmol/L vs 2.66±0.82 mmol/L,P<0.01).治疗24 wk后,各组ALT和GGT较治疗前无明显变化.结论:ω-3多不饱和脂肪酸胶丸在改善非酒精性脂肪肝肝脏B超评分方面有明显作用,尤其是高剂量组作用尤为显著,且高剂量药物对血清甘油三脂的改善也有一定作用.     

ω-3多不饱和脂肪酸对肝癌细胞的影响研究现状

ω-3多不饱和脂肪酸在预防和治疗癌症上有着重要的作用,可以诱导细胞凋亡,并在一定程度上降低癌细胞的侵袭力。随着对多不饱和脂肪酸研究的不断深入,发现ω-3多不饱和脂肪酸可抑制肝癌细胞的增殖并诱导其凋亡,但其机制尚不明确。本文就ω-3多不饱和脂肪酸与癌症的关系、对肝癌细胞凋亡的影响及其作用机制作简要阐述。     

ω-3多不饱和脂肪酸对HepG2细胞胆固醇代谢的影响

目的胆固醇是维持哺乳动物细胞存活及功能所不可缺少的成分,然而高水平的血清胆固醇是动脉硬化性心血管疾病的独立危险因素。体内胆固醇代谢的平衡取决于以下三个主要代谢途径:体内胆固醇的合成、小肠对胆固醇的吸收以及胆汁/粪便胆固醇的分泌等。因此,降低体内胆固醇的合成,减少胆固醇的吸收,以及增加胆固醇的分泌都是降低体内胆固醇水平的有效手段。已有研究报道ω-3多不饱和脂肪酸(ω-3 PUFA)可以增加小鼠巨噬细胞胆固醇的流出而促进胆固醇的逆向转运。但ω-3 PUFA对肝细胞胆固醇代谢的影响至今未见报道。本研究旨在探讨ω-3 PUFA在肝细胞胆固醇合成和分泌中的作用。方法应用50μmol/Lω-3 PUFA(DHA或EPA)处理人肝癌细胞系HepG2 48 h后,收集细胞,用甲醇/氯仿(2∶1)溶液抽提细胞总脂质,在表面活性剂TritonX-100的作用下将脂质溶解于蒸馏水中,并用酶法测定细胞胆固醇浓度;提取细胞总蛋白,用Western blot检测与胆固醇合成相关基因SREBP2和HMG-CoA还原酶,胆固醇向胆酸转化的限速酶CYP7a1,以胆固醇分泌相关基因ABCG8的蛋白表达情况。结果经50μmol/LDHA或EPA处...     

Extending the cardiovascular benefits of omega-3 fatty acids

The cardiovascular benefits of omega (n)-3 fatty acids (FA) become clearer with each passing year. Although useful in large doses for lowering serum triglyceride levels, the primary benefits are likely to arise from smaller, nutritional intakes of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA). Doses of less than 1 g/d appear to reduce risk for fatal coronary heart disease events, perhaps by stabilizing the myocardium and reducing risk for fatal arrhythmias. New evidence points to a possible benefit on atrial fibrillation, particularly in the immediate post-cardiac surgery setting. Studies in women with coronary heart disease now suggest that plaque progression may be slowed by increased intakes of oily fish, even in women with diabetes. The relative importance of the n-6 FA linoleic acid (LA), the short-chain n-3 FA alpha linolenic acid (ALA), and the long-chain n-3 FAs EPA and DHA is becoming clearer. If intakes of the latter are adequate (perhaps over 250 mg/d), then there appears to be little need to consume more ALA or less LA.     

The role of omega-3 fatty acids in cardiovascular disease

Plant-derived alpha-linolenic acid has been studied in a limited number of investigations. So far, some epidemiologic and a few mechanistic studies suggest a potential of protection from cardiovascular disease, but this potential remains to be proven in intervention studies. In contrast, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are prevalent in fish and fish oils, have been studied in thousands of investigations. A consistent body of evidence has been elaborated in various types of investigations, ultimately demonstrating reduction in total mortality, cardiovascular mortality, and morbidity by ingestion of roughly I g/d of EPA plus DHA. Current guidelines, however, do not discern between the omega-3 fatty acids mentioned; in fact, most even do not differentiate polyunsaturated fatty acids at all. Unfortunately, this complicates efficient implementation of an effective means of prophylaxis of atherosclerosis.     

New evidence for the cardiovascular benefits of long chain omega-3 fatty acids

The role of long chain omega-3 fatty acids (LC n-3 FAs) as cardioprotective agents has become even clearer with the recent publication of the Japan EPA Lipid Intervention Study. This was the largest randomized controlled trial in the field, and it demonstrated that even in a population with one of the highest LC n-3 FA intakes in the world, the addition of eicosapentaenoic acid could reduce cardiac events. A comprehensive analysis of the risks and benefits of fish consumption was likewise recently published that should quiet any remaining fears that there are substantial risks to consuming oily fish such as salmon. A new meta-analysis has now demonstrated that reduced tissue/blood levels of LC n-3 FAs provide a better indication of increased cardiovascular risk than the n-6:n-3 ratio. Finally, a supplementation study in cardiac surgery patients has demonstrated both the time course and extent of incorporation of LC n-3 FAs into the human heart.     

Cardiovascular benefits of omega-3 fatty acids

Cardiac societies recommend the intake of 1 g/day of the two omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for cardiovascular disease prevention, treatment after a myocardial infarction, prevention of sudden death, and secondary prevention of cardiovascular disease. These recommendations are based on a body of scientific evidence that encompasses literally thousands of publications. Of four large scale intervention studies three also support the recommendations of these cardiac societies. One methodologically questionable study with a negative result led a Cochrane meta-analysis to a null conclusion. This null conclusion, however, has not swayed the recommendations of the cardiac societies mentioned, and has been refuted with good reason by scientific societies. Based on the scientific evidence just mentioned, we propose a new risk factor to be considered for sudden cardiac death, the omega-3 index. It is measured in red blood cells, and is expressed as a percentage of EPA + DHA of total fatty acids. An omega-3 index of >8% is associated with 90% less risk for sudden cardiac death, as compared to an omega-3 index of <4%. The omega-3 index as a risk factor for sudden cardiac death has striking similarities to LDL as a risk factor for coronary artery disease. Moreover, the omega-3 index reflects the omega-3 fatty acid status of a given individual (analogous to HbA1c reflecting glucose homeostasis). The omega-3 index can therefore be used as a goal for treatment with EPA and DHA. As is the case now for LDL, in the future, the cardiac societies might very well recommend treatment with EPA and DHA to become goal oriented (e.g. an omega-3 index>8%).     

Omega-3多不饱和脂肪酸抗心律失常作用及其机制研究进展

越来越多的研究表明,n-3多不饱和脂肪酸（n-3PUFAs）能降低心率,提高心率变异性,减少室性心律失常的发生,预防心源性猝死及减少心房颤动复发等抗心律失常作用,也有研究发现n-3PUFAs具有致心律失常的作用。本文通过分析n-3PUFAs离子通道作用特点及其抗心律失常作用机制,发现n-3PUFAs干预方式不同,作用机制不完全一样,表明n-3PUFAs在抗心律失常方面具有两面性。     

Effects of omega-3 polyunsaturated fatty acids on depression

Depression is characterised by depressed mood or/ and the loss of interest or pleasure in nearly all activities for a substantial period of time, causing significant distress. Depression is a potentially life-threatening disease. It is a major risk factor for suicide as well as coronary artery disease (CAD) and sudden cardiac death (SCD). It also may be associated with impaired endothelial dysfunction and decreased heart rate variability (HRV). Both conditions seem to persist in patients with depression despite successful antidepressant treatment. During the last few years epidemiological studies as well as clinical trials have suggested a significant role of omega-3 fatty acids in the pathogenesis of depression. As omega-3 fatty acids have been demonstrated to also beneficially influence many of the conditions depression is a risk factor for (CAD, SCD) or may be associated with (decreased HRV, endothelial dysfunction), they may well represent a major advance in the treatment of depression. However more large randomized clinical trials are clearly needed to substantiate that claim.