他汀类药物对动脉粥样硬化斑块稳定与消退的作用

动脉粥样硬化斑块破裂是动脉粥样硬化相关性缺血性卒中(AT-IS)的主要发病机制。而通过医学干预使粥样硬化斑块保持稳定甚至消退,则是针对AT-IS进行一级和二级预防治疗的新靶点,也是标志其预防是否成功的关键。动物研究发现,炎症不仅贯穿于动脉粥样硬化的形成与进展、粥样硬化斑     

当归抗家兔主动脉粥样硬化形成的作用

为观察中药当归注射液对家兔实验性主动脉粥样硬化形成的影响并探讨其可能的作用机制。将 18只家兔随机分为正常对照组、模型组和当归组 3组 ;分别给予普通饲料 (正常对照组 )和高脂饲料 (其它两组 )喂养 ;当归组动物在喂高脂饲料的同时 ,加当归注射液。喂养第 10周末颈动脉放血取血样后 ,处死动物 ,检测血脂、主动脉粥样硬化斑块面积和血清丙二醛含量。结果发现 ,当归组动物血中甘油三酯水平显著降低 (P <0 .0 1) ,但总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇均无变化。同时当归组动物主动脉斑块面积显著小于模型组 (P <0 .0 1)。当归组动物血清丙二醛含量也显著低于模型组 ,但仍比对照组高 (P <0 .0 1)。实验结果提示 :当归注射液具有抗家兔主动脉粥样硬化形成的作用 ;这种作用与它降低血清甘油三酯水平、抗脂质过氧化有关。     

小剂量普伐他汀对颈动脉内膜动脉粥样硬化斑块的影响

目的探讨小剂量普伐他汀(10mg)对颈动脉内膜动脉粥样硬化斑块的作用及时效关系。方法42例冠心病患者随机分为A、B两组，给予普伐他汀10mg／d，A组服药8周，B组服药12周，治疗前后检测颈总动脉、颈内动脉内膜粥样硬化斑块并计算斑块面积，同时观察血脂水平变化。结果两组分别治疗8、12周后，TC、TG、LDL-C水平均显著降低，HDL-C水平显著升高，颈动脉内膜斑块面积显著缩小，但两组间比较无显著差别。结论普伐他汀10mg治疗8周后可显著缩小颈动脉内膜斑块并显著降低血脂水平，且方便安全，对于预防急性心脑血管事件有着特殊的临床意义。     

小剂量普伐他汀对颈动脉内膜动脉粥样硬化斑块的影响

目的：探讨小剂量普伐他汀（10mg)对颈动脉内膜动脉粥样硬化斑块的作用及时效关系。方法：42例冠心病患者随机分为A、B两组，给予普伐他汀10mg/d，A组服药8周，B组服药12周，治疗前后检测总动脉、颈内动脉内膜粥样硬化斑块并计算斑块面积，同时观察血脂水平变化。结果：两组分别治疗8、12周后，TC，TG、LDL－C水平均显著降低，HDL－C水平显著升高，颈动脉内膜斑块面积显著缩小，但两组间比较无显著差异。结论：普伐他汀10mg治疗8周后可显著缩小颈动脉斑块并显著降低血脂水平，且方便安全，对于预防急性心脑血管事件有着特殊的临床意义。     

电针对实验家兔颈动脉粥样硬化斑块VCAM-1的影响

目的探讨电针治疗后血管细胞间黏附分子-1(VCAM-1)在兔颈动脉粥样硬化斑块中表达的影响。方法采用空气干燥法加高脂饲料喂养制备兔颈动脉粥样硬化斑块模型,电针组选取大椎、天门(风府)、风池(双侧)、丰隆(双侧)、足三里(双侧)进行治疗,以模型组、药物组作为对照,同时设立空白组。免疫组化法检测颈动脉粥样硬化斑块组织中VCAM-1的表达。结果电针使VCAM-1在家兔颈动脉粥样硬化斑块中的表达减少,电针组与模型组比较差异有统计学意义(P<0.01)。结论电针可能是通过减少VCAM-1在家兔颈动脉粥样硬化斑块中的表达来稳定动脉粥样硬化斑块的,是电针治疗颈动脉粥样硬化斑块的可能作用机制之一。     

丹参对粥样斑块Bax、Bcl-2和MCP-1、IL-6含量的影响

目的研究丹参抑制动脉粥样硬化形成的分子机制。方法建立动脉粥样硬化家兔模型,比较对照组、AS组及丹参组动脉粥样斑块形成的变化;免疫组化结合RT-PCR法分析Bcl-2、Bax及MCP-1、IL-6在粥样硬化斑块中的表达。结果丹参组血脂水平和动脉粥样斑块面积低于AS组(P<0.01);免疫组化显示,AS组Bcl-2、Bax及MCP-1、IL-6阳性细胞表达与正常组有显著差异。而丹参的干预可以调节Bax/Bcl-2阳性细胞表达率,同时下调MCP-1蛋白表达。结论丹参抑制动脉粥样硬化斑块的形成;调节Bcl-2/Bax表达及炎症机制可能是抗动脉粥样硬化的机制之一。     

辛伐他汀、阿司匹林治疗颈动脉粥样硬化斑块疗效观察

用辛伐他汀、阿司匹林并辅以低胆固醇饮食及适量运动的方法治疗颈动脉粥样硬化，服药前后记录颈动脉管腔直径以及颈内外动脉粥样硬化斑块的数量、大小、内中膜厚度。结果治疗1．5～4a后，患者颈动脉粥样硬化斑块体积缩小或消失，认为该方法是稳定和消退动脉粥样硬化斑块的有效方法。     

选择性环氧化酶-2抑制剂对载脂蛋白E基因敲除小鼠动脉粥样硬化影响的实验研究

目的:观察选择性环氧化酶-2抑制剂对载脂蛋白E基因敲除小鼠动脉粥样硬化进展的影响。方法:8周龄载脂蛋白E基因敲除小鼠分为塞来昔布(celecoxib)组及安慰剂组,均予高脂饮食喂养,分别以特异性环氧化酶-2抑制剂塞来昔布及安慰剂灌胃8周;同龄野生型小鼠为正常对照组。酶法分析测定血脂,油红O染色观察主动脉根部粥样硬化斑块大小。结果:塞来昔布组与安慰剂组之间实验前后血脂水平均无差异,但均高于正常对照组(胆固醇水平P<0.01,甘油三酯水平P<0.05)。油红O染色显示,塞来昔布组及安慰剂组可见明显粥样硬化斑块形成;前者的斑块面积及斑块面积/原管腔面积均较后者显著降低(P均<0.01)。结论:用选择性环氧化酶-2抑制剂塞来昔布进行抗炎干预可抑制动脉粥样硬化的进展,其机制与调脂无关。针对炎症机制有望有效控制动脉粥样硬化的发生发展。     

糖调节受损与脑梗死患者颈动脉粥样硬化不稳定斑块的相关性研究

目的 观察糖调节受损与脑梗死患者颈动脉粥样硬化斑块不稳定性的相关性.方法 动脉粥样硬化性脑梗死患者139例,根据颈动脉彩色多普勒超声显像分为颈动脉粥样硬化不稳定斑块组60例、颈动脉粥样硬化稳定斑块组79例.所有患者均进行空腹血糖测定和糖耐量试验,结合患者颈动脉粥样硬化斑块、血脂水平和糖调节受损情况,分析糖调节受损在颈动脉粥样硬化不稳定斑块形成中的相关性.结果 颈动脉粥样硬化不稳定斑块组中糖调节受损者所占比例比颈动脉粥样硬化稳定斑块组高(P＜0.05,P＜0.01),其致动脉粥样硬化斑块不稳定作用与脂质代谢紊乱相关.结论 糖调节受损参与并促进颈动脉粥样硬化不稳定斑块的形成.可通过早期干预血糖调节防治脑梗死.     

FTO基因敲低对动脉粥样硬化斑块内Th细胞的影响

目的拟建立兔动脉粥样硬化模型,在动脉粥样硬化斑块上敲低FTO基因,了解动脉粥样硬化内Th细胞的变化。方法将30只健康新西兰大白兔随机分成3组,每组兔均将其股动脉进行球囊扩张受损,造成动脉粥样硬化模型,给予高脂喂养9 w后,A组行假手术,B组于股动脉粥样硬化处注射病毒空载体(GFP),C组于股动脉粥样硬化处注射AAV9-FTO敲低病毒。1 w后处死取出股动脉粥样硬化组织。结果股动脉粥样硬化组织行Western印迹发现C组FTO表达水平较A、B组明显下降;行病理HE染色,发现C组炎症反应较A、B组明显加重;行流式细胞发现C组CD3+CD4+T细胞占T细胞的比例明显上升(P<0.05)。结论建立兔动脉粥样硬化斑块FTO敲除模型,证明FTO敲除对动脉粥样硬化斑块T细胞稳定性有影响。     

Comparative beneficial effects on platelet functions and atherosclerosis of dietary linoleic and gamma-linolenic acids in the rabbit

Male rabbits (10 weeks old) were fed, for 20 weeks, purified diets rich in fat (45% of calories) containing saturated fats (butter), polyunsaturated fats (evening primrose oil + butter or sunflower oil + butter) for 20 weeks. Linoleic acid represented respectively 3.6, 33 and 34% of the dietary fatty acids, while gamma-linolenic acid was present (4.4%) solely in the second group. A significant increase in di-homo-gamma-linolenic acid in plasma, platelets and aorta was noted only in the animals fed evening primrose oil. Despite this, the results of the platelet aggregation to thrombin and ADP, the recalcification plasma-clotting time (platelet-rich plasma) and the severity of atherosclerosis were not significantly different from those observed in the group fed sunflower oil. In contrast, in comparison to the butter-fed animals, the two groups fed the polyunsaturated fats showed remarkable improvements in the clotting time (P less than 0.01) and in the severity of atherosclerotic lesions (evening primrose oil P less than 0.001; sunflower oil P less than 0.05). However, the response to thrombin-induced aggregation was significantly decreased (P less than 0.05) only in the evening primrose oil-fed animals. In these long-term studies in young rabbits, dietary gamma-linolenic acid did not seem to have marked beneficial effects, additional to those induced by linoleic acid, on platelet functions or on atherosclerosis.     

Release of fatty acids by perfused vascular tissue in normotensive and hypertensive rats

The release of fatty acids from perfused mesenteries of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was studied. The release of the prostaglandin precursors dihomogammalinolenic acid, arachidonic acid, and eicosapentaenoic acid was reduced in SHR when compared with age-matched WKY. The release of all other fatty acids detected in the effluent was also reduced. The differences in fatty acid release were evident even when tissue levels of the fatty acids were similar or higher in SHR than in controls. The addition of evening primrose oil and fish oil into the diet partially corrected these defects. Evening primrose oil and fish oil both attenuated increases in blood pressure, but fish oil was more potent than primrose oil. Although both diets reduced vascular reactivity, primrose oil was more effective with lower doses of norepinephrine whereas fish oil blunted the effects of both low and high doses of norepinephrine. The possible mechanisms for the effects of primrose oil and fish oil on vascular reactivity are briefly discussed.     

The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects

OBJECTIVE: Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years. METHODS: In a double-blind, randomised, placebo controlled study, 173 healthy volunteers took one of six oil supplements for 8 months. Supplements were placebo, oleic acid rich sunflower oil, evening primrose oil, soya bean oil, tuna fish oil, and tuna/evening primrose oil mix. Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside, respectively. RESULTS: Acetylcholine, but not sodium nitroprusside responses were significantly improved after tuna oil supplementation (P=0.02). Additionally, there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation. No significant changes in vascular response were seen after supplementation with any of the other oils. CONCLUSIONS: Fish oil supplementation has a beneficial effect on endothelial function, even in normal healthy subjects. Modification of the diet by an increase of 6% in eicosapentaenoic acid and 27% in docosahexaenoic acid (equivalent to eating oily fish 2-3 times/week) might have significant beneficial effects on cardiovascular function and health.     

Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids.

The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids.     

Influence of different dietary fatty acid sources on erythrocyte lipids and plasma and liver essential fatty acids in hamsters fed ethanol

Hamsters fed ethanol were given three different dietary sources of essential fatty acids; safflower oil, evening primrose oil (both mainly n-6 fatty acids) or linseed oil (mainly n-3 fatty acids). After 7 weeks, plasma, erythrocyte and liver lipids and fatty acids were analyzed. Plasma and liver lipids were not significantly different in the ethanol-fed hamsters compared to the controls. Erythrocyte total phospholipid was increased only in the ethanol-fed groups given n-6 but not n-3 fatty acids. Some fatty acid changes induced by ethanol were predictable, e.g. lower 20:4 n-6 in hamsters fed n-6 fatty acids, but others were not predictable, e.g. higher 22:6 n-3 in all the ethanol-fed groups. The effect of ethanol on hamster lipids and fatty acid composition appears dependent on the predominant class of dietary fatty acids.     

Effects of gammalinolenic acid on plasma lipoproteins and apolipoproteins

Nineteen hypercholesterolemic patients (10 without and 9 with hypertriglyceridemia) were given evening primrose oil rich in gammalinolenic acid (GLA, 18: 3n - 6), in a placebo controlled cross-over design, over 16 weeks (8 + 8 weeks), with safflower oil as the placebo. During supplementation with evening primrose oil, dihomogammalinolenic acid (20: 3n - 6) increased in plasma lipids and red blood cells, and in subjects without hypertriglyceridemia there was a significant decrease in low density lipoprotein-cholesterol and plasma apolipoprotein B compared with the levels observed during safflower oil administration. Our results confirmed that evening primrose oil is effective in lowering low density lipoprotein in hypercholesterolemic patients.     

Essential fatty acid treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus

Summary In rats with 6 weeks streptozotocin-diabetes there was a 53% reduction in sciatic nerve laser Doppler flux compared to controls (p<0.01). Treatment of a parallel group of diabetic rats with evening primrose oil, by dietary admixture throughout the protocol, prevented this ischaemia (Doppler flux was 91% of evening primrose oil-treated controls and was not significantly different). There were no differences in systemic arterial pressure. In another experiment evening primrose oil markedly antagonised the development of exaggerated resistance to anoxic conduction failure in sciatic nerves from diabetic rats. The resistance to anoxia of nerves from non-diabetic rats was also reduced by evening primrose oil. These observations suggest that the sciatic nerves of diabetic rats with short-term streptozotocin-diabetes are markedly ischaemic and that this ischaemia is involved in the development of increased resistance to anoxic/ischaemic conduction failure in diabetic nerve. The findings also promote evening primrose oil as a potential treatment to prevent nerve ischaemia.     

Effects of gamma-linolenic acid supplementation on pregnant rats fed a zinc-deficient diet

The effects of dietary gamma-linolenic acid supplementation in the form of evening primrose oil were examined in pregnant zinc-deficient rats and subsequently in their newborn pups. This supplementation was beneficial, since it reduced pup mortality, increased mean litter size and maintained appetite throughout two thirds of the gestation period. Consequently, gamma-linolenic acid seems to correct some of the biological effects of zinc deficiency. It is suggested that evening primrose oil could be used in cases of zinc deficiency caused by metabolic disturbances.     

Interactions between essential fatty acid,prostanoid, polyol pathway and nitric oxide mechanisms in the neurovascular deficit of diabetic rats

Summary Impaired -6 essential fatty acid metabolism and exaggerated polyol pathway flux contribute to the neurovascular abnormalities in streptozotocin-diabetic rats. The potential interactions between these mechanisms were examined by comparing the effects of threshold doses of aldose reductase inhibitors and evening primrose oil, alone and in combination, on neurovascular deficits. In addition, highdose aldose reductase inhibitor and evening primrose oil treatment effects were challenged by co-treatment with the cyclo-oxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, N^G-nitro-l-arginine. Eight weeks of diabetes caused an 18.9% reduction in sciatic motor conduction velocity (p<0.001). This was only modestly ameliorated by a 0.1% dietary supplement of evening primrose oil or the aldose reductase inhibitors ZD5522 (0.25 mg · kg^–1 · day^–1) and WAY121509 (0.2 mg · kg^–1· day^–1) for the final 2 weeks. However, joint treatment with primrose oil and ZD5522 or WAY121509 caused marked 71.5 and 82.4% corrections, respectively, of the conduction deficit. Sciatic nutritive blood flow was 43.1% reduced by diabetes (p<0.001) and this was corrected by 67.8% with joint ZD5522 and primrose oil treatment (p<0.001). High-dose WAY121509 (10 mg · kg^–1 · day^–1) and primrose oil (10% dietary supplement) prevented sciatic conduction velocity and nutritive blood flow deficits in 1-month diabetic rats (p<0.001). However, these effects were abolished by flurbiprofen (5 mg · kg^–1 · day^–1) and N^G-nitro-l-arginine (10 mg · kg^–1 · day^–1) co-treatment (p<0.001). Thus, the data provide evidence for synergistic interactions between polyol pathway/nitric oxide and essential fatty acid/cyclo-oxygenase systems in the control of neurovascular function in diabetic rats, from which a potential therapeutic advantage could be derived.Abbreviations ARI Aldose reductase inhibitor - EPO evening primrose oil - NCV nerve conduction velocity - NO nitric oxide - NOLA N^G-nitro-l-arginine     

Essential fatty acid treatment — effects on nerve conduction,polyol pathway and axonal transport in streptozotocin diabetic rats

Summary This study was designed to examine the effect of dietary supplementation with essential fatty acids (evening primrose oil — 5% weight:weight added to the diet) on acute neurophysiological and neurochemical defects in streptozotocin-diabetic rats. Diabetic rats, which were not given evening primrose oil, showed highly significant elevations of nerve sorbitol and fructose combined with a depletion of nerve myo-inositol. In those animals there was also a 40% reduction (p<0.02) in the accumulation of axonally transported substance P-like immunoreactivity proximal to a 12 h sciatic nerve ligature together with reduced motor nerve conduction velocity (13% [p<0.001] and 20% [p<0.001] in two separate experiments). Treatment of other diabetic rats with evening primrose oil prevented completely the development of the motor nerve conduction velocity deficit without affecting sorbitol, fructose or myo-inositol levels or the deficit in axonal transport of substance P. In a second experiment, treatment of diabetic rats with evening primrose oil was associated with significant attenuation of the conduction velocity deficit, but not complete prevention.