多不饱和脂肪酸对成年雪貂心肌钾通道的作用

本研究是在成年雪貂的心肌上研究多不饱和脂肪酸（PUFA）对电压门控钾通道的效应。我们观察到,n-3 PUFA能抑制短时性外向钾电流（Ito)和延迟整流钾电流（IK),而对内向整流钾电流（IK1）则没有明显影响。二十二碳六烯酸（DHA）对Ito和Ik能产生浓度依赖性的抑制作用,其IC50分别为7.5和20μmol/L,但不影响IK1。二十碳五烯酸（EPA）对这三种钾通道的作用与DHA相似。花生四烯酸（5或10μmol/L)先引起IK的抑制,然后引起IK,AA的激活;用环氧合酶抑制剂消炎痛可以阻断花生四烯酸激活IK,AA的作用。不具有抗心律失常作用的单不饱和脂肪酸和饱和脂肪酸都不明显影响这些钾通道的活性。上述实验结果证明,n-3 PUFA能抑制心肌细胞的Ito和IK,但和我们以前报道的PUFA对心肌钠电流和钙电流的作用相比,其对Ito和IK抑制作用的效能较低。n-3 PUFA的抗心律失常效应可能与它们抑制心肌钠、钙、钾通道的作用有关。     

多不饱和脂肪酸对人体的作用

多不饱和脂肪酸又叫多烯酸,是指分子结构中含有２个或２个以上不饱和双键的脂肪酸。双键愈多,不饱和程度愈高,营养价值也愈高［１］。随着科学的发展,某些多不饱和脂肪酸对人体的作用进一步被认识,特别是以廿二碳六烯酸、廿碳五烯酸和一般植物油中的亚油酸（常与亚麻...     

钾通道在大鼠支气管平滑肌张力调控中作用的研究

目的：探讨延迟整流钾通道（Kv),高电导钙激活钾通道（BKCa)和ATP敏感钾通道（KATP)在大鼠支气管平滑肌张力调控中的作用。方法：以特异性钾通道阻断剂为工具,采用体外等长张力测定观察钾通道对静息和收缩状态下支气管张力的影响。结果：（1）KV阻断剂4－aminopyridine(4-AP)诱发大鼠支气管平滑肌产生浓度依赖性收缩反应,而BKCa阻断剂tetraethylammonium(TEA)和KATP阻断剂glibenclamide(Glib)对其无影响。（2）去除上皮对4－AP诱发大鼠支气管平滑肌收缩反应无影响,而钙通道阻断剂nifedipine对其有显著抑制效应。（3）在0.1mmol/L组胺或50mmol/L KCl诱发支气管平滑肌收缩之前或之后,加入TEA（1,5mmol/L)或0.1mmol/L 4-AP均显著增强二者诱发的收缩反应;而Glib(10μmol/L）对其无明显影响。结论：Kv参与大鼠支气管平滑肌静息张力的调控,而BKCa和KATP对其无影响。Kv和BKCa的关闭增强组胺及高浓度钾离子诱发大鼠离体支气管产生的收缩张力。     

心肌细胞钾通道的分子学多样性

电压调控性钾通道和内向整流性钾通道是心肌细胞两类主要的钾通道,对心肌细胞动作电位的形成起重要的作用。对其分子生物学结构的多样性的研究,有助于进一步弄清其功能并为寻找理想的抗心律失常药物提供理论指导。     

BKCa通道的结构与功能

BKCa通道将细胞膜电特性与细胞信号系统联系在一起,在细胞功能实现中起着重要作用。该通道广泛且又较高密度地表达于许多物种的多种组织,其分子结构复杂,丰富的超家族成员具有各自不同的表达分布。BKCa通道的分子结构由α亚单位和β亚单位构成,其中α亚单位形成通道的孔道区和活性调节区域,β亚单位修饰通道活性的调节特性。BKCa通道开放几率大、电导率高、调控位点多,并且不同的超家族成员表现出不同的功能特征,如细胞膜电位感受性、细胞内游离钙离子敏感性等。文章概述BKCa通道的分子结构和功能特征。     

钾通道活化剂对豚鼠气道平滑肌电压依赖性钾通道特性的影响

钾通道活化剂可激活钾离子通道并松驰支气管平滑肌,在急性分离的豚鼠支气管平滑肌细胞上,用膜片钳技术的细胞贴附式和内面向外式研究了其对电压依赖性钾通道的直接作用。结果证实：在全细胞记录条件下,卡吗克林和拉吗克林不影响静息膜电位。但在去极化时可使通道电导从７５．２±５．１ｐＳ分别增大到８５．９±１１．８ｐＳ和８２．１±５．５ｐＳ。通道动力学特性也发生了改变,通道平均开放时间的τｏ２值延长和开放概率显著增加,其中拉吗克林的作用更为强。两者均可诱发通道出现多级开放。表明这两类活化剂可使去极化时钾离子外流增加。     

心室钾通道电流对室性心律失常的影响及调控

本文采用犬心室外膜细胞模型,仿真模拟了不同剂量药物阻滞钾通道电流(iKr和iKs)对室性心律失常产生的影响及调控作用。结果发现,适当阻滞钾电流可减轻室性心律失常,甚至使心律恢复正常。然而,若药物剂量使用过大,过度阻滞钾电流,则会引起早期后除极(earlyafterdepolarization,EAD)的产生,导致室性心律失常症状的加重。此时,我们可以通过调节细胞外钠离子浓度([Na+]o)和晚钠电流(iNaL)等方法来减轻或消除这种负面影响。     

新型钾通道开放剂对心血管ATP-敏感性钾通道基因表达的调节作用

目的：研究脂肪胺类的新型钾通道开放剂（KCO）埃他卡林（Ipt）和氰胍类的KCO吡那地尔（Pin）对大鼠心血管ATP-敏感性钾通道（KATP）的亚基SUR1、SUR2、Kir6．1和Kir6．2等在mRNA水平的调节作用。方法：SD大鼠给药1周后处死并取组织,提取总RNA,利用反转录-聚合酶链式反应（RT-PCR）研究以上基因在mRNA水平的改变。结果：与正常对照相比,心脏组织中,Ipt和Pin对KATP的4个亚基在mRNA水平均无显著影响;主动脉平滑肌上,Ipt对4个亚基的mRNA表达无显著影响,但Pin可显著上调SUR2的mRNA表达;尾动脉平滑肌上,Ipt对Kit6．1／Kit6．2、Pin对SUR2／Kir6．1均有显著下调的作用。结论：心肌、大动脉平滑肌和小动脉平滑肌KATP基因表达的调控不同,Ipt选择性调节小动脉平滑肌Kit6．1／Kit6．2;Ipt对心血管KATP基因表达的调节作用不同于Pin。     

电压门控性钾通道的结构和调控机制

电压门控性K 通道是由4个相同亚单位构成的四聚体通道,其中每个亚单位都含有1个电压感受器,并且4个亚单位合起来组成1个中央孔.电压门控性通道蛋白具有3种主要功能,一是离子通透功能,二是门控蛋白构象改变,三是门控与感知机制的偶联.通道具有高通透速率和高选择性,通过构象改变的门控机制有3种,一是S6束交叉门控,二是球链门控,三是选择性滤器的门控.     

核糖体肽链输出通道对基因表达的调控作用

核糖体大亚基上的肽链输出通道起始于肽酰转移酶中心附近,横穿大亚基,主要由rRNA和少量蛋白质组成,是新生肽链离开大亚基的通道,近年研究发现这是通道的一个动态的结构,它不仅能够与新生肽链中的效应模体相互作用翻译效率,而且能够调节通过通道的多肽链的共翻译折叠,修饰,还可协助它们在细胞中定位。     

Polyunsaturated Fatty Acid Modulation of Voltage-Gated Ion Channels

Arachidonic acid (AA) was found to inhibit the function of whole-cell voltage-gated (VG) calcium currents nearly 16 years ago. There are now numerous examples demonstrating that AA and other polyunsaturated fatty acids (PUFAs) modulate the function of VG ion channels, primarily in neurons and muscle cells. We will review and extract some common features about the modulation by PUFAs of VG calcium, sodium, and potassium channels and discuss the impact of this modulation on the excitability of neurons and cardiac myocytes. We will describe the fatty acid nature of the membrane, how fatty acids become available to function as modulators of VG channels, and the physiologic importance of this type of modulation. We will review the evidence for molecular mechanisms and assess our current understanding of the structural basis for modulation. With guidance from research on the structure of fatty acid binding proteins, the role of lipids in gating mechanosensitive (MS) channels, and the impact of membrane lipid composition on membrane-embedded proteins, we will highlight some avenues for future investigations.     

植物合成长链多不饱和脂肪酸研究进展

长链不饱和脂肪酸（LC-PUFAs）对人类健康具有重要作用,通过转基因植物生产LC-PUFAs具有低成本、可持续、污染少等诸多优势。本文简要介绍了LC-PUFAs的作用、来源及其植物生物合成途径,综述了转基因植物合成LC-PUFAs的研究进展,并对如何进一步提高LC-PUFAs产量进行了探讨。     

Enzymatic Esterification of Long Polyunsaturated Fatty Acids and Lyso-Phosphatidylcholine in Isooctane and Ethanol

Phosphatidylcholine (PC) was synthesized from lyso-PC and long poly-unsaturated (n-3) fatty acids (PUFA) using immobilized phospholipase A₂. The esterification was performed using the fatty acids as the main solvent and isooctane or ethanol (99.5%) at low concentrations (7–45%) as additional solvents. The temperature was kept constant at 45d`C and the water concentrations were carefully controlled.

The best yield of PC (22%) was found in the isooctane system at a low water content (22% of the dry immobilized enzyme). In the ethanol system, the yield of PC was only half. The best yields were attained when the concentrations of both isooctane and ethanol were below 7% and the reaction time was very long (9 days). Improved contact between the enzyme and the substrates would probably increase the reaction rate.     

富含不饱和脂肪酸饲料对大鼠血液学指标及主要脏器的影响

目的探讨富含不饱和脂肪酸饲料对SD大鼠血液学指标及主要脏器的影响。方法以富含不饱和脂肪酸的青花椒籽油饲料饲喂断乳SD大鼠60d,试验结束时测定部分血清学和血液细胞学指标及脑、心脏、肝脏、肾脏、脾脏系数,并对心脏、肝脏、肾脏进行病理学观察。结果实验组雄性大鼠与正常对照组同性别大鼠相比,甘油三脂和低密度脂蛋白显著降低（P〈0．05）,实验组饲料极显著提高雄性大鼠大脑系数,极显著提高雄性和雌性大鼠肝脏和肾脏系数（P〈0．01）;心脏、肝脏、肾脏病理学观察结果为阴性。结论富含不饱和脂肪酸饲料对大鼠血清学指标有一定影响,对大鼠心、肝、。肾组织无明显影响。     

Enzymatic and Non-Enzymatic Esterification of long Polyunsaturated Fatty Acids and Lysophosphatidylcholine in Isooctane

Phosphatidylcholine containing large amounts of long polyunsaturated fatty acid, eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6), was synthesized in isooctane. Immobilized phospholipase A₂ was used as a catalyst. A parallel non-enzymatic esterification reaction was investigated in separate experiments.

The concentrations of lyso-phosphatidylcholine, polyunsaturated fatty acids, water and the enzyme were varied over wide ranges as were the temperature and the reaction time. The type of enzyme, carrier and immobilization procedure were held constant.

The yield of phosphatidylcholine was relatively high (about 21%) when the concentration of polyunsaturated fatty acids was high (300 mg/g of reaction mixture) and the water content was low (below 30% of the dry immobilized enzyme). The highest yield of phosphatidylcholine was found at 80 hours and 75°C. However, at this temperature an extensive non-enzymatic reaction between polyunsaturated fatty acids and lyso-phosphatidylcholine occurred. At 80°C the polyunsaturated fatty acids were partly oxidized. Therefore, a temperature of 45°C to 65°C is probably the optimum temperature for the reaction.     

细菌通过聚酮合成酶途径合成多不饱和脂肪酸的研究进展

细菌利用聚酮合成酶途径合成多不饱和脂肪酸是近年发现的新的脂肪酸合成途径。这种途径与常规的由脂肪酸去饱和酶和脂肪酸延长酶引导的脂肪酸合成途径有着本质上的差别。总结了近些年细菌利用聚酮合成酶合成多不饱和脂肪酸这一新途径的研究状况,重点阐明其分子机制,并对其研究趋势及应用前景进行了展望。     

The Benefits and Risks of n-3 Polyunsaturated Fatty Acids

There is a growing number of animal models and clinical trials of n-3 polyunsaturated fatty acid (PUFAs) supplementation in disease. Epidemiologic and biochemical studies have suggested beneficial effects of n-3 PUFAs. But also, the use of n-3 PUFAs has some potential toxicological risks that can be circumvented by careless processing, storing, and preserving the PUFAs. The use of n-3 PUFAs is safe if appropriate preparations and dosages are selected. Much research is needed to clarify their use under different disease conditions. The newly established clinical and nutritional facts on n-3 PUFAs will induce industry to develop food products based on this knowledge.     

ω-3 多不饱和脂肪酸对PTSD-SPS 大鼠行为学影响的研究

目的:观察饲料中添加ω-3PUFAs对PTSD-SPS大鼠焦虑/抑郁行为的防护作用。方法:将40只健康成年雄性SD大鼠随机分为正常对照组、PTSD-SPS模型组、60%ω-3PUFAs+PTSD-SPS模型组1、60%ω-3PUFAs+PTSD-SPS模型组2。采用高架十字迷宫实验和旷场实验评价实验组大鼠的焦虑/抑郁行为变化。结果:与对照组相比,SPS模型组大鼠进入开放臂的次数比例和时间比例明显减少;中央格停留时间明显缩短(5.56±0.21)s,穿格次数明显减少(30.23±5.96)次,差异均显著(P<0.05)。与SPS模型组相比,60%ω-3PUFAs的SPS组大鼠进入开放臂的次数比例和时间比例明显增加;中央格停留时间明显延长(9.88±1.14)s,穿格次数明显增加(43.22±4.35)次,差异均显著(P<0.05);与对照组相比没有显著差异。结论:膳食补充ω-3多不饱和脂肪酸可以降低PTSD-SPS大鼠焦虑/抑郁程度。     

Metabolic Engineering of Plants to Produce Very Long-chain Polyunsaturated Fatty Acids

Very long-chain polyunsaturated fatty acids (VLCPUFAs) are essential for human health and well-being. However, the current sources of these valuable compounds are limited and may not be sustainable in the long term. Recently, considerable progress has been made in identifying genes involved in the biosynthesis of VLCPUFAs. The co-expression of these genes in model systems such as plant embryos or yeast provided many valuable insights into the mechanisms of VLCPUFA synthesis. The recent successful reconstitution of pathways leading to the synthesis of arachidonic acid, eicosapentaenoic acid and finally docosahexaenoic acid in oil-seed plants indicates the feasibility of using transgenic crops as alternative sources of VLCPUFAs. The various approaches used to attain these results and the specific constraints associated with each approach are discussed.