卡托普利对家兔实验性动脉粥样硬化的抑制作用

目的：探讨卡托普利对平滑肌细胞增生、移行、动脉硬化形成和发展 的影响,并进一步研究动脉粥样硬化（AS）的发病机制和AS家兔模型的制作方法。方法：选择日本大耳白兔利用高脂、高胆固醇膳食法建立AS模型,制作过程中动态观察血胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）水平。实验结束后处死动物做病理学检查（光镜和电子显微镜）,并做AS面积的测定。结果：卡托普利和硒维尔＋VE联合用药可抑制TG及LDL的升高,而对HDL和TC影响不大。AS斑块面积的测定以预防组最小。病理电镜片可见动脉硬化组内皮细胞坏死、脂质沉积,SMC以合成表型为主,硒维尔＋VE联合用药内皮改变轻,卡托普利预防组内膜良好无明显泡沫细胞,SMC以收缩型为主。结论：卡托普利对AS发生、发展的重要因素LDL、平滑肌细胞移和增生、平滑细胞从收缩型向合成型转化等均有抑制作用。     

氨氯地平抗兔动脉粥样硬化的实验研究

目的　观察氨氯地平的抗动脉粥样硬化 (AS)效应并探讨其机制。方法　将 32只大耳白兔随机分为 :对照组、模型组、硝苯地平治疗组、氨氯地平治疗组 ,每组 8只兔分别给予普通饲料、高脂饲料、高脂饲料 +硝苯地平、高脂饲料 +氨氯地平喂养 6 0d ,试验前、中、后测定血浆和红细胞的脂质、脂质过氧化物、红细胞膜流动性 (M Flu)、血浆内皮素 (ET)、全血血小板活化因子 (PAF)以及血小板聚集率 (PAR)水平 ,实验后取心脏、主动脉、肝脏作组织生化和病理学检查。结果　氨氯地平与硝苯地平作用类似 ,可降低血中ET、PAF水平 ,升高高密度脂蛋白胆固醇 (HDL C)水平 ,减少肝脏、主动脉以及红细胞膜胆固醇含量 ,抑制血液和组织的脂质过氧化损伤 ,保护血管内皮细胞和红细胞的功能 ,调整血管平滑肌细胞的表型并抑制其增殖 ,降低血小板聚集活性。结论　氨氯地平和硝苯地平具有显著的抗动脉粥样硬化作用。     

转换酶抑制剂和长效钙拮抗剂对实验性动脉硬化防治作用的对比研究

目的　探讨卡托普利和氨氯地平对动脉硬化家兔模型的预防治疗作用。方法　动态观察各模型组血胆固醇 ,甘油三酯 ,低密度脂蛋白 ,高密度脂蛋白水平 ,测各组动脉硬化面积及光镜、电镜切片的观察。结果　卡托普利和硒 VE可抑制甘油三酯和低密度脂蛋白 ,氨氯地平可抑制胆固醇 ,升高高密度脂蛋白水平 ,卡托普利预防动脉粥样硬化 (AS)作用比氨氯地平强 ,且可抑制 SMC从收缩型向合成型转化。结论　早期应用转化酶抑制剂和长效钙拮抗剂均可抑制 AS的发生、发展 ,且以转换酶抑制剂效果佳。     

衰老因素对动脉粥样硬化大鼠血脂等指标的影响

目的观察亚急性衰老联合动脉粥样硬化模型在血脂等方面与动脉粥样硬化模型的区别。方法 2月龄健康雄性SD大鼠随机分为正常组、AS组、AS+衰老组和衰老组。14 w后处死、取材,测定血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、氧化型低密度脂蛋白(oxLDL)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量,根据公式计算动脉硬化指数(AI)值,并进行比较。结果与正常组相比,其余各组TC、TG、LDL、oxLDL、AI水平升高(P<0.05),AS+衰老组HDL含量降低(P<0.05),各组SOD水平降低(P<0.05)。与AS组比较,AS+衰老组TC、LDL、oxLDL、AI水平升高(P<0.05),HDL-C、SOD含量降低(P<0.05)。结论在AS模型基础上加入D-半乳糖干预造成一定程度的老化可加剧AS模型大鼠TG、TC、LDL、HDL、oxLDL、MDA、SOD指标的变化。     

培哚普利对家兔实验性动脉粥样硬化的防治研究

目的：研究培哚普利对动脉粥样硬化形成和发展的影响。方法：实验家兔设立对照组，动脉粥样硬化组，培哚普利动脉粥样硬化预防组，培哚普利动脉粥样硬化治疗组，从血脂，光镜，电镜及对动脉粥样硬化相关因素内皮素（ET），脂质过氧化物（LPO），一氧化氮（NO），肿瘤坏死因子（TNF），白细胞介素－6（IL－6）等方面进行观察。结果：实验发现培哚普利可抑制胆固醇（TC），甘油三酯（TG）及低密度脂蛋白（LDL）的升高，以预防用药作用最明显，同时升高高密度脂蛋白（HDL），动脉粥样硬化斑声面积的测定以预防组最小，和其余组比较有显著性差异，从光镜及电镜片中可见培哚普利可抑制平滑肌细胞（SMC）增生和移行，用药组平滑肌细胞以收缩型为主。另外有提高NO，降低ET，LPO，TNF，IL－6的作用。结论：培哚普利具有预防和早期治疗动脉粥样硬化的作用。     

玉米苞叶对动脉粥样硬化家兔平滑肌细胞凋亡及p53和Fas蛋白表达的影响

目的：探讨玉米苞叶防治动脉粥样硬化（AS）的机制。方法：选用大耳白家兔，复制家兔AS模型，随机分为动脉粥样硬化模型组，玉米苞叶组和正常对照组，成模后给予玉米苞叶煎剂治疗，8w后处死家兔，采用流氏细胞术检测平滑肌细胞的凋亡率以及凋亡相关基因p53和Fas蛋白表达。结果：模型组血管平滑肌细胞的凋亡率明显高于对照组（P＜0．05），p53和Fas蛋白的表达增强（P＜0．05），主动脉壁肉眼观测出现典型斑块。玉米苞叶组平滑肌细胞的凋亡率明显低于模型组（P＜0．05），p53和Fas蛋白表达下调（P＜0．05）；主动脉斑块面积较模型组明显减小，结论：玉米苞叶通过调节p53和Fas蛋白表达而调节AS家兔平滑肌细胞凋亡。     

白黎芦醇对AS模型大鼠主动脉bcl-2及caspase-3表达影响的研究

目的 观察白黎芦醇对动脉粥样硬化(AS)模型大鼠主动脉壁平滑肌细胞bcl-2和caspase-3 mRNA表达的影响.方法 雄性SD大鼠复制食饵性AS早期模型,用药组灌胃白藜芦醇70 mg/(kg·d)共4 w.造模给药用逆转录聚合酶链反应,观察对照组、模型组和用药组主动脉壁平滑肌细胞bcl-2和caspase-3 mRNA的表达.结果 白藜芦醇组通过影响AS早期主动脉壁平滑肌细胞bcl-2和caspase-3表达,阻止AS的进程.结论 白藜芦醇对大鼠动脉粥样硬化具有保护作用,并能提高AS斑块稳定性.     

动脉粥样硬化治疗的新策略-载脂蛋白A-I类似物蛋白肽

动脉粥样硬化(atherosclerosis,AS)是危及生命的最常见心血管疾病之一,目前在预防和治疗方面仍缺乏明显有效的药物。过去曾认为AS是胆固醇储积疾病,但随着近十年的不断深入研究,目前发现AS不是一种局部性的疾病,而是一种炎症紊乱性疾病,这为寻找AS的药物预防和治疗方法提供新的思路。研究认为,低密度脂蛋白(low density lipoprotein,LDL)的增加是引起AS的主要原因,氧化LDL更是AS的主要危险因素,而高密度脂蛋白(high densitylipoprotein,HDL)的增加则具有预防AS功能,特别是HDL的主要功能蛋白——载脂蛋白A-I(apolipopro-tein A-I…     

复方丹参滴丸对家兔动脉粥样硬化的影响

目的：探讨复方丹参滴丸对家兔实验性动脉粥样硬化（AS）的抑制作用。方法：设正常对照组、AS组和复方丹参滴丸组，测定血脂（TC、TG、LDL－C和HDL－C)含量及NO与ET水平，并进行统计学处理。结果：复方丹参滴丸对血脂有明显的改善或调节作用，P＜0.05或P＜0.01；在AS组中，复方丹参滴丸组NO水平明显高于AS组，ET水平则明显低于AS组，P＜0.01或P＜0.001。结论：复方丹参滴丸对AS组血脂、NO和ET水平有明显的改善或调节作用。     

氧化低密度脂蛋白损伤血管内皮细胞与平滑肌细胞增殖相关性研究

氧化修饰低密度脂蛋白(oxidized low-densitylipoprotein,ox-LDL)损伤血管内皮细胞(VEC)是动脉粥样硬化(AS)形成的重要因素之一。VEC结构和功能的损伤及血管平滑肌细胞(VSMC)增殖和迁移是AS形成及发展过程中重要的病理生理改变。流行病学资料表明,血脂水平高于正常与AS的发生及冠心病(CHD)的发病率有密切的相关性,从而明确高脂血症是AS及CHD的危险因素。许多学者认为,VEC结构和功能损伤是AS发生的始动环节,VSMC增殖和迁移是AS发生及发展的关键病理环节。人们在预防和治疗AS过程中,不仅要着眼于改善低密度脂蛋白(LDL)的氧…     

Intermediate density lipoprotein levels are strong predictors of the extent of aortic atherosclerosis in the St. Thomas's Hospital rabbit strain

This study assessed nonfasting cholesterol and triglyceride in plasma and in lipoproteins as predictors of the extent of aortic atherosclerosis in 2 similar groups of rabbits from the St. Thomas's Hospital strain; the lipoprotein classes studied in the 2 groups were very low (VLDL), intermediate (IDL), low (LDL), and high density lipoprotein (HDL), and Sf greater than 60 lipoprotein, Sf 12-60 lipoprotein, LDL and HDL, respectively. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL, with plasma cholesterol and triglyceride of up to 23 mmol/l and 7 mmol/l, respectively, and with up to 100% of the aortic intima bearing atherosclerosis-like lesions. In group 1 rabbits (n = 25), univariate linear regression showed that cholesterol in plasma, LDL, IDL and in VLDL each were positively associated with the extent of aortic atherosclerosis. In group 2 rabbits (n = 20), cholesterol in plasma, LDL and Sf 12-60, but not in Sf greater than 60 lipoprotein, was consistently positively associated with the extent of aortic atherosclerosis. Neither plasma triglyceride, triglyceride in lipoprotein fractions nor HDL cholesterol was associated consistently with the extent of atherosclerosis. Using step-up multiple linear regression among lipoprotein lipids, IDL and Sf 12-60 lipoprotein cholesterol were the most powerful independent predictors of the extent of aortic atherosclerosis in the 2 groups of rabbits. LDL cholesterol was the only other independent predictor. The results suggest that remnant lipoproteins, whether defined as IDL or Sf 12-60 lipoprotein, play an important causal role in atherosclerosis under conditions where plasma levels of these lipoproteins are elevated.     

Primary prevention of atherosclerosis by lovastatin in a genetically hyperlipidaemic rabbit strain

Lovastatin, a lipid-lowering drug which inhibits cholesterol synthesis, was administered to genetically hyperlipidaemic rabbits from the age of 2 months. Twenty rabbits were selected with similar plasma cholesterol levels and divided into matched treatment and control groups. The treated animals showed a 60% decrease in plasma cholesterol due to reduced levels of low density lipoprotein (LDL) and intermediate density lipoprotein (IDL). Levels of other lipoproteins remained unchanged. In untreated animals cholesterol levels in plasma, LDL and IDL increased with age. The area of aortic atherosclerosis-like lesions was quantified after 2-10.5 months of treatment. At each time point the extent of arterial disease was profoundly less in treated than in untreated animals. The findings demonstrate that primary prevention of arterial lesions resembling human atherosclerosis (increased amounts of fibrous tissue, smooth muscle cell proliferation, foam cell formation and necrosis at the base of the plaques) results from early effective reduction of elevated plasma lipids by lovastatin in this rabbit strain.     

Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis

The oxidation of low-density lipoproteins (LDL) plays an important role in the development of atherosclerosis. Curcumin is a yellow pigment obtained from rhizomes of Curcuma longa and is commonly used as a spice and food colouring. Curcumin and turmeric extracts have several pharmacological effects including antitumour, anti-inflammatory, antioxidant and antiinfectious activities although the precise mechanisms involved remain to be elicited. We evaluated the effect of an ethanol-aqueous extract obtained from rhizomes of C. longa on LDL oxidation susceptibility and plasma lipids in atherosclerotic rabbits. A total of 18 rabbits were fed for 7 weeks on a diet containing 95.7% standard chow, 3% lard and 1. 3% cholesterol, to induce atherosclerosis. The rabbits were divided into groups, two of which were also orally treated with turmeric extract at doses of 1.66 (group A) and 3.2 (group B) mg/kg body weight, respectively. A third group (group C) acted as a control. Plasma and LDL lipid composition, plasma alpha-tocopherol, plasma retinol, LDL TBARS, LDL lipid hydroperoxides and analysis of aortic atherosclerotic lesions were assayed. The low but not the high dosage decreased the susceptibility of LDL to lipid peroxidation. Both doses had lower levels of total plasma cholesterol than the control group. Moreover, the lower dosage had lower levels of cholesterol, phospholipids and triglycerides in LDL than the 3.2-mg dosage. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.     

Amlodipine attenuates oxidative stress in the heart and blood of high-cholesterol diet rabbits

Introduction

Oxidative stress is a key component of atherosclerosis. It has been suggested that amlodipine inhibits oxidative stress. In this study, we evaluated the effects of amlodipine on the total antioxidant capacity of heart tissue and blood in 36 control and cholesterol-fed male New Zealand white rabbits.

Methods

The rabbits were divided into four groups (n = 9). Group 1 rabbits were fed a regular diet, group 2 were fed a diet with 2% cholesterol, group 3 were fed a regular diet plus 5 mg/kg/day oral amlodipine, and group 4 were fed 2% cholesterol diet plus amlodipine 5 mg/kg/day. At the end of eight weeks, blood samples were drawn and at the same time heart tissue was isolated and frozen in liquid nitrogen. After homogenisation, the solution was centrifuged and the light supernatant was stored at –80˚C. This was used for determination of glutathione peroxidase (GPX), superoxide dismutase (SOD) and (MDA) levels.

Results

Eight weeks of amlodipine treatment significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides in the group on the hypercholesterolaemic diet (p < 0.05). In the blood, the level of thiobarbituric acid-reactive substances increased in the rabbits on the 2% cholesterol diet (group 2) and 2% cholesterol-plusamlodipine diet (group 4) and decreased in the amlodipineonly group (group 3) (p < 0.05). Lipid peroxidation in the heart tissue was similar to that in the blood, except in the amlodipine-only group (group 3). In the blood, the activity of total SOD (tSOD) decreased in the group on the 2% cholesterol diet (group 2) (p < 0.05) and markedly increased in the amlodipine-only (group 3) and 2% cholesterol-plusamlodipine groups (group 4) (p < 0.05).

Conclusion

Amlodipine decreased oxidative stress in the heart and blood and improved the lipid profile in cholesterolfed rabbits. Therefore, it may be considered a useful tool for the reduction of oxidative stress and improvement of lipid profiles in diseases related to atherosclerosis.     

氨氯地平对高脂血症家兔红细胞膜脂质过氧化物及膜流动性的效应

目的 :观察氨氯地平 (Aml)对高脂血症家兔红细胞膜脂质过氧化物及膜流动性的效应。方法 :2 4只家兔随机分为对照组、模型组、治疗组 ,分别给予普通饲料、高脂饲料以及高脂饲料加Aml连续喂 6 0d ,喂养前后分别采空腹耳中央动脉血 5ml测定红细胞膜脂质、脂质过氧化物 (LPO)、抗氧化酶以及膜流动性。结果 :高脂饲料喂养的家兔能诱导其红细胞膜低密度脂蛋白胆固醇 (M LDLC)、膜共轭双烯 (M CD)以及红细胞丙二醛 (E MDA)水平升高 ,红细胞膜流动性 (M Flu)以及红细胞超氧化物歧化酶 (E SOD)水平降低 ,而Aml可以防止高脂饲料所诱导的M LDLC、M CD、E MDA水平进一步升高 ,并能防止M Flu水平进一步降低。结论 :Aml具有抗红细胞膜脂质过氧化损伤 ,改善M Flu的作用。     

依那普利、硝苯吡啶和洛伐他汀对家兔实验性动脉粥样硬化的影响

为探讨依那普利、硝苯吡啶和洛伐他丁对高胆固醇兔动脉粥样硬化的影响,本文将３７只新西兰雄性白兔随机分为正常饮食组、胆固醇组、依那普利组、硝苯吡啶组和洛伐他丁组,后三组在高胆固醇饮食的基础上给相应药物。喂养１６周后处死所有动物,测定主动脉组织中胆固醇含量及斑块面积比。结果发现,依那普利和硝苯吡啶不影响血脂水平,洛伐他丁有降低胆固醇,甘油三脂及低密度脂蛋白的作用,洛伐他丁组低密度脂蛋白／高密度脂蛋白的比     

The role of fibric acid derivatives in the secondary prevention of coronary heart disease

Fibric acid derivatives effectively lower triglycerides and raise high-density lipoprotein (HDL) cholesterol, but their effect on low-density lipoprotein (LDL) cholesterol is weakly beneficial (small decreases) to adverse (small increases) and varies according to the triglyceride level. Early primary prevention studies of atherosclerosis using the fibric acid derivative clofibrate showed only modest effects on atherosclerosis and an alarming increase in mortality in the intervention group. Although the Helsinki Heart Study later demonstrated that gemfibrozil decreased cardiac endpoints in primary prevention without increasing total mortality, the efficacy of fibric acid derivatives in both primary and secondary prevention of atherosclerosis has remained widely in doubt. Nevertheless, many patients with atherosclerosis have normal or even low LDL cholesterol, but elevated triglyceride, and low HDL cholesterol; furthermore, even aggressive LDL cholesterol lowering with HMG Co-A (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) fails to prevent the majority of atherosclerotic events. These findings have kindled increased interest in the use of fibric acid derivatives in atherosclerosis prevention, especially through treatment of non-LDL dyslipidemias. Recent studies with angiographic and clinical end-points have now provided evidence for a beneficial effect of at least some drugs in this class in the secondary prevention of atherosclerosis.