n-3多不饱和脂肪酸类抗心律失常的作用

二十多年前,Ｂａｎｇ和Ｄｙｅｒｂｅｒｇ提出爱斯基摩人较低的心血管病死亡率可能与他们食用含高浓度的多不饱和脂肪酸类(ＰＵＦＡｓ)的海生食物有关。随后的研究表明该物质具有预防和减少动脉粥样硬化形成等生化和生理作用。晚近,在临床应用ＰＵＦＡｓ抗动脉粥样硬化治疗过程中,发现令人鼓舞现象,即这些ＰＵＦＡｓ在短期内可以显著地降低病人心脏性猝死的发生率,提示其具有直接的抗心律失常作用。ＰＵＦＡｓ主要包括ｎ3ＰＵＦＡｓ和ｎ6ＰＵＦＡｓ,前者如二十碳五烯酸(Ｃ20:5ｎ3,ＥＰＡ)、二十二碳六烯酸(Ｃ22:6ｎ3,ＤＨＡ)和α亚麻酸(Ｃ18:…     

Omega-3多不饱和脂肪酸代谢产物的动脉粥样硬化拮抗机制

动脉粥样硬化是由内皮细胞的损伤、脂质沉积等引起的慢性炎症反应性病理过程。Omega-3多不饱和脂肪酸(n-3 PUFA)具有重要的动脉粥样硬化保护作用,但其机制仍不明确。多不饱和脂肪酸在环氧化酶、脂氧合酶和细胞色素P450氧化酶的作用下产生具有不同生物活性的类二十烷酸代谢产物。Omega-3多不饱和脂肪酸在自身被代谢为类二十烷酸的同时,也可与花生四烯酸竞争共同的代谢酶,从而也对花生四烯酸来源的类二十烷酸代谢产物水平起调控作用。文章基于代谢的观点,系统地讨论了Omega-3多不饱和脂肪酸通过影响类二十烷酸代谢谱而发挥动脉粥样硬化拮抗作用的机制。     

n-3多不饱和脂肪酸对坏死性小肠结肠炎保护作用的机制研究

目的 探讨n-3多不饱和脂肪酸对坏死性小肠结肠炎(NEC)保护作用的机制.方法 将30只3日龄的C57BL/6J乳鼠随机分成DF组、NEC组及n-3补充组(n=10).观察每组小鼠NEC发生情况与严重程度;组织学检测乳鼠肠道组织损伤情况;采用ELISA检测乳鼠肠组织IL-1β和TNF-α的分泌水平;利用qRT-PCR与...     

n-3多不饱和脂肪酸对室性心律失常发生的影响及其机制

越来越多的证据表明n-3多不饱和脂肪酸可降低室性心律失常的发生,其机制主要包括抑制炎症和氧化应激,改善心肌细胞电生理、心室结构重构和自主神经功能等。深入探讨n-3不饱和脂肪酸对室性心律失常发生的影响及其机制,可为室性心律失常的防治提供新策略。     

鱼油n-3多不饱和脂肪酸抗动脉粥样硬化研究进展

本文主要综述鱼油ｎ－３多不饱和脂肪酸对血脂和脂蛋白的影响及抗动脉粥样硬化的效应。     

非传统抗心律失常药物的研究进展

尽管导管射频消融技术越来越多应用于临床,但药物治疗仍然是目前防治心律失常的重要手段.近年来随着对各种心律失常发生机制研究的不断深入,以及各项大规模临床试验的开展,非传统抗心律失常药物的作用日益受到重视.我们对具有潜在抗心律失常作用的非抗心律失常药物的研究进展及地位进行综述.     

抗心率失常药物的致心律失常作用

本文缩述各种抗心律失常药物致心律失常作用的发生率，发生机理，识方法及处理原则，对临床正确运用抗心律失常物具有指导意义。     

索他洛尔的抗心律失常作用机制

索他洛尔(Sotalol)于1960年合成．最初是作为β受体阻滞剂用于治疗高血压及心绞痛。嗣后发现该产品除β阻滞作用外，还具有很强的抗心律失常作用，故于1970年起分类Ⅱ类抗心律失常药(即延长动作电位时间药物)，迄今应用于心律失常治疗已10余年。     

抗心律失常药物的致心律失常作用

抗心律失常药物的致心律失常作用是指抗心律失常药物在某些患者中应用时,在特定病程中或在特定的临床情况下出现用药前没有的新的心律失常或使原有心律失常更加恶化.有的抗心律失常药致心律失常作用后果严重,如不及时处理可危机生命,增加病死率.因此,在抗心律失常治疗过程中,正确及时识别抗心律失常药的致心律失常作用并采取相应对策有着非常重要的临床意义.     

Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate?

The objective of this blinded, randomized, prospective study was to assess whether supplementation of normal diet with omega-3 polyunsaturated fatty acids can reduce angiographically defined restenosis following coronary angioplasty. The study included all patients undergoing coronary angioplasty in this institution between January 1988 and January 1989. One hundred and twenty patients enrolled, 60 in each treatment group. All were randomized to either supplementation of normal diet with 3 g of omega-3 polyunsaturated fatty acids per day started 1-2 days prior to angioplasty and continued for 6 months (treatment group), or to receive standard therapy only (control group). Quantitative angiographically defined restenosis was assessed at 6 months post angioplasty. Restenosis occurred in 27.8% (95% CI 18.0-37.7%) of lesions in the treatment group and in 28.3% (CI 16.9-39.7%) of lesions in the control group, but the difference was not statistically significant. The study showed that diet supplemented with 3 g of omega-3 polyunsaturated fatty acids started 1-2 days preceding angioplasty does not reduce angiographically defined restenosis rate.     

omega-3多不饱和脂肪酸治疗非酒精性脂肪性肝病的研究进展

随着人们生活方式和饮食结构的改变,非酒精性脂肪性肝病(NAFLD)发病率逐年上升,严重威胁人类健康。NAFLD疗法一直是基础和临床肝病研究的热门领域。近年来,诸多研究揭示omega-3多不饱和脂肪酸(ω3-PUFA)可促进脂肪酸氧化并改善肠道稳态,从而改善脂代谢和肝脏炎症,因而越来越多的临床研究开始将ω3-PUFA运用于NAFLD的治疗中。然而,ω3-PUFA治疗NAFLD的机制尚不明确,相关临床研究也存在一定局限性。主要介绍了ω3-PUFA在NAFLD中发挥的作用以及相关的临床研究结果,并进一步讨论ω3-PUFA治疗NAFLD尚需解决的问题。     

Omega-3 long-chain polyunsaturated fatty acids support aerial insectivore performance more than food quantity

Once-abundant aerial insectivores, such as the Tree Swallow (Tachycineta bicolor), have declined steadily in the past several decades, making it imperative to understand all aspects of their ecology. Aerial insectivores forage on a mixture of aquatic and terrestrial insects that differ in fatty acid composition, specifically long-chain omega-3 polyunsaturated fatty acid (LCPUFA) content. Aquatic insects contain high levels of both LCPUFA and their precursor omega-3 PUFA, alpha-linolenic acid (ALA), whereas terrestrial insects contain much lower levels of both. We manipulated both the quantity and quality of food for Tree Swallow chicks in a full factorial design. Diets were either high-LCPUFA or low in LCPUFA but high in ALA, allowing us to separate the effects of direct LCPUFA in diet from the ability of Tree Swallows to convert their precursor, ALA, into LCPUFA. We found that fatty acid composition was more important for Tree Swallow chick performance than food quantity. On high-LCPUFA diets, chicks grew faster, were in better condition, and had greater immunocompetence and lower basal metabolic rates compared with chicks on both low LCPUFA diets. Increasing the quantity of high-LCPUFA diets resulted in improvements to all metrics of performance while increasing the quantity of low-LCPUFA diets only resulted in greater immunocompetence and lower metabolic rates. Chicks preferentially retained LCPUFA in brain and muscle when both food quantity and LCPUFA were limited. Our work suggests that fatty acid composition is an important dimension of aerial insectivore nutritional ecology and reinforces the importance of high-quality aquatic habitat for these declining birds.Aerial insectivores, a paraphyletic group that includes the swallows, swifts, nightjars, and at least five different families of flycatchers, were once abundant throughout both temperate and tropical regions. However, in the last half century, a number of North American aerial insectivores across a diversity of families and species, ranging from Common Nighthawks (Chordeiles minor) and Chimney Swifts (Chaetura pelagica) to Olive-sided Flycatchers (Contopus cooperi) and Tree Swallows (Tachycineta bicolor), have undergone major declines (1, 2). For example, Tree Swallows, one of the best-studied model aerial insectivore taxa in North America, have declined by 36% over the past 2 to 3 decades (2). Experts have proposed several hypotheses, including (i) declines in aerial insects (3), (ii) habitat loss and degradation (3–5), (iii) environmental contaminants (6, 7), and (iv) climate change and phenological mismatch (8, 9). Evidence exists to support all of these hypotheses, yet, at present, the exact causes of aerial insectivore declines remain unresolved, pointing to the need for a more thorough understanding of all aspects of aerial insectivore ecology.Past studies have documented the importance of food resources for aerial insectivores, and numerous studies have suggested that aerial insectivore declines are linked to decreasing overall insect abundance (e.g., ref. 1). Research on Tree Swallows shows that food availability is linked with chick growth rates and fledging success as well as egg size and composition (10, 11). Winkler et al. (11) found that environmental temperature had a strong effect on patterns of Tree Swallow chick mortality, most likely through its effect on insect activity levels. However, the sheer quantity of food resources may not be the only important factor. Food quality and the potential for mismatch between insect composition and the nutritional needs of aerial insectivores may also be important drivers of reproductive output and overall fitness for these birds (e.g., ref. 12).Food quality can be defined in many ways, including caloric density, nutrient composition, and digestibility (13). Here, we focus on differences in composition of macronutrients. Aerial insectivores, like all animals, require organic compounds [e.g., vitamins, amino acids, and fatty acids (FAs)] in addition to elemental nutrients (e.g., nitrogen, phosphorus, and calcium) to grow, develop, and complete their life cycles. Omega-3 long-chain polyunsaturated FAs (LCPUFA), in particular the FAs docosahexaenoic acid (22:6n-3, DHA) and eicosapentaenoic acid (20:5n-3, EPA), are especially important organic compounds for most animals, affecting a range of important physiological processes, from immune function to vision and brain development (14). Birds and all other vertebrates must either consume EPA and DHA directly from diet or indirectly by consuming their molecular precursor, the short-chain omega-3 PUFA, alpha linolenic acid (18:3n-3, ALA), and then converting ALA into EPA and DHA. The capability of any particular animal species to convert ALA to the bioactive EPA and DHA depends on whether its diet contains EPA and DHA (14). Mammalian herbivores typically synthesize all EPA and DHA endogenously from ALA, whereas carnivores such as cats must obtain all of their DHA from diet (15). The ability of wild birds to synthesize DHA is not well characterized, but DHA concentrations are inversely related to mass (16). For example, DHA constitutes 12% of FAs in the muscles of House Sparrows (Passer domesticus) (16), which are similar in size to Tree Swallows, but can reach over 20% in Ruby-throated Hummingbird (Archilochus colubris) muscle (17).In the wild, aerial insectivores consume a combination of terrestrial and aquatic insects (18), which differ in their FA composition (19). Aquatic insects contain much higher levels of LCPUFA than do terrestrial insects, a difference driven by differences in the FA composition of aquatic and terrestrial primary producers (19, 20). Aquatic primary producers, such as diatoms and dinoflagellates, are rich in EPA and DHA (21), which can be incorporated into aquatic insect tissue (22). In contrast, vascular terrestrial plants contain little to no LCPUFA but do contain their molecular precursor ALA (14), which can be either incorporated into tissue or converted to LCPUFA to a minor degree by terrestrial insects (19). As a consequence, from the perspective of LCPUFA content, aquatic insects may constitute a higher-quality food for aerial insectivores than do terrestrial insects.However, because both aquatic and terrestrial insects contain ALA, the relative value of aquatic insects depends on the capacity of aerial insectivores to convert ALA into LCPUFA (19). The ability to elongate ALA into LCPUFA varies greatly across taxa: Strict carnivores, such as cats (23, 24), and animals from environments rich in LCPUFA, including most marine fish (25), have lost the ability to elongate ALA into LCPUFA and must obtain them directly from diet. In contrast, terrestrial herbivores appear to be relatively efficient at converting ALA to LCPUFA (26). The capacity of aerial insectivores to convert ALA to LCPUFA remains untested, but, as predators living around riparian areas with emergent aquatic insects rich in LCPUFA, they appear likely to be limited by LCPUFA content in diet.The majority of past studies on avian FA requirements have focused on domesticated herbivorous taxa, especially chickens (e.g., refs. 27 and 28). These studies found domestic hens to be relatively efficient at elongating ALA, EPA, and DHA (e.g., refs. 27 and 28). Far fewer studies have experimentally manipulated dietary FA composition for wild birds (but see refs. 29–32). These studies have found that both dietary composition and elongation capacity of individual species affect avian FA composition (32). However, with the exception of work by Pierce et al. (31) on Red-Eyed Vireos (Vireo olivaceus), these studies have either looked at seed- and fruit-eating passerines or fish-eating seabirds. To our knowledge, no studies have explicitly examined the omega-3 FA requirements of any aerial insectivores. Therefore, we sought to understand the importance of food FA composition for aerial insectivores by varying both food quality and quantity in a balanced factorial experimental design.In nature, the effects of food quality and quantity may be confounded because parents may provide chicks with an increased quantity of food to make up for low-quality food. To address this, we experimentally manipulated both the quantity and FA composition of food for wild-hatched nestling Tree Swallow chicks. Chicks were fed one of four diets: (i) a high-LCPUFA, high-quantity diet containing EPA and DHA (Hh); (ii) a low-LCPUFA, high-quantity diet containing high ALA and low omega-3 LCPUFA (Lh); (iii) a high-LCPUFA, low-quantity diet (Hl); and (iv) a low-LCPUFA, low-quantity diet (Ll). We assessed size-specific growth rates, body condition, immunocompetence, and basal metabolic rates (BMR) as metrics of performance. We also determined the FA composition of brain and breast muscle tissue from a subset of chicks from each treatment group.     

Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids

Summary Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production, increased blood viscosity in association with impaired cell deformability and pathologic leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries. Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 205 in total fatty acids, and a reduction of the thromboxane_2/3 ratio from 600 (untreated diabetic rats) to 50 (treated diabetic rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group (115.1±26.8; untreated diabetic 65.2±15.0 acellular capillary segments/mm² of retinal area). We conclude from this study that dietary fish oil supplementation may be harmful for the diabetic microvasculature in the retina.Abbreviations EPA Eicosapentaenoic acid - STZ streptozotocin - AGE advanced glycation end products - TxB thromboxane - AU arbitrary units - PMN polymorphonuclear neutrophil granulocytes - RP-HPLC reverse-phase-high performance liquid chromatography     

Perioperative omega-3 fatty acids for liver surgery: A meta-analysis of randomized controlled trials

Introduction:The effect of perioperative omega-3 fatty acids for liver surgery remained controversial. We conducted a systematic review and meta-analysis to explore the influence of omega-3 fatty acids versus placebo in patients undergoing liver surgery.Methods:We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020, and included randomized controlled trials (RCTs) assessing the effect of omega-3 fatty acids versus placebo for liver surgery. This meta-analysis was performed using the random-effect model.Results:Five RCTs were included in the meta-analysis. Overall, compared with control group for liver surgery, omega-3 fatty acids were associated with substantially reduced incidence of infection (odd ratio [OR]=0.56; 95% confidence interval [CI] =0.34–0.91; P = .02), but revealed no remarkable influence on complications (OR = 0.60; 95% CI = 0.29–1.24; P = .17), mortality (OR = 0.76; 95% CI = 0.06–9.37; P = .83), liver failure (OR = 0.72; 95% CI = 0.10 to 5.00; P = 0.74), biliary leakage (OR=1.24; 95% CI = 0.41 to 3.76; P = .70), bleeding (OR = 1.76; 95% CI = 0.63–4.95; P = .28), or ileus (OR = 0.39; 95% CI = 0.07–2.05; P = .27).Conclusion:Perioperative omega-3 fatty acids may be beneficial to reduce the incidence of infection after liver surgery.     

Omega-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia

Epidemiological studies have established an association between high triglycerides (TG) plasma levels and increased cardiovascular risk. Increased TG levels, commonly coupled with low HDL-C levels, are common in high cardiovascular risk subjects including those with dyslipidemia, metabolic syndrome and type 2 diabetes. Management of hypertriglyceridemia (HTG) includes lifestyle modification for mild-to-moderate HTG and pharmacological therapies for the treatment of high and very high TG levels. Among drugs, fibrates, nicotinic acid and omega-3 polyunsaturated fatty acids may be considered. Omega-3 fatty acids reduce plasma TG levels by several mechanisms; beside the effects on TG, omega-3 can also influence the levels of other lipids and lipoproteins including HDL-C and LDL-C. Clinical trials have also shown that omega-3 fatty acid supplementation is effective also when added in combination with other lipid-lowering drugs. These findings suggest that omega-3 fatty acids may be usefully considered for the management of high TG levels.     

n-3 polyunsaturated fatty acids prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model

Objective

It has been recently reported that atrial fibrillation (AF) is associated with inflammation and inflammatory cytokines, and n-3 polyunsaturated fatty acids (PUFAs) might be of anti-inflammatory effects. This study was to evaluate the anti-inflammatory effect of PUFAs on AF in a canine sterile pericarditis model.

Methods

20 dogs were randomly assigned to two groups: control group (10 dogs) and PUFA treatment group (10 dogs), in which sterile pericarditis was created by open-chest operation. PUFAs were administered orally (2 g/day) 4 weeks before the operation till the end of the study. Before and 2 days after the operation, CRP, IL-6, TNF-α levels, the inducibility and maintenance of AF, the atrial effective refractory period (AERPs), and intra-atrial conduction time were determined.

Results

Before the operation, there were no significant differences in any of the parameters between the two groups. On the second postoperative day, the PUFA group had a lower CRP level (7.6 ± 0.5 vs. 11.7 ± 1.3 mg/dl, P < 0.0001), a lower IL-6 level (112.0 ± 37.3 vs. 142.0 ± 19.6 pg/ml, P < 0.01), a lower TNF-α level (83.3 ± 8.5 vs. 112.4 ± 8.2 pg/ml, P < 0.0001), a less AF inducibility (percentage of burst attempts leading to AF episodes: 11 ± 7.4 vs. 28 ± 10.3, P < 0.001) and maintenance [median AF duration: 1105 s (655.8-1406.5) vs. 2516.5 s (1187-3361), P < 0.05], a longer AERP (133.4 ± 4.1 vs. 129.8 ± 4.3 ms, P < 0.05), and a shorter intra-atrial conduction time (46.6 ± 4.4 vs. 51.9 ± 4.8 ms, P < 0.05) than the control group.

Conclusions

Dietary n-3 PUFA supplementation attenuates the inducibility and maintenance of AF in the sterile pericarditis model by reducing the production of proinflammatory cytokines.     

Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease

BACKGROUND AND AIM: There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD). METHODS AND RESULTS: Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F. CONCLUSIONS: For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.     

Clinical pharmacology of n-3 polyunsaturated fatty acids: non-lipidic metabolic and hemodynamic effects in human patients

A high dietary intake of n-3 long chain polyunsaturated fatty acids (PUFA), eicosapentaenoic and docosahexaenoic acids, is associated with a reduced incidence of coronary events. Supplementation with pharmacological doses of the same may improve survival in patients with previous myocardial infarction and established heart failure. Such protective effects may be explained by the action of n-3 PUFA on systemic inflammation, hypertension, endothelial dysfunction, thrombosis, cardiac arrhythmias, heart rate variability and atherosclerotic plaque instability, which are involved in the pathogenesis of these clinical conditions. In this short paper we will review the evidence in support of these pleiotropic effects of n-3 fatty acids.