辛伐他汀对兔动脉粥样硬化血管平滑肌层CPT-1的表达影响

目的观察三羟基三甲基辅酶A(HMG-CoA)还原酶抑制剂-辛伐他汀对兔动脉粥样硬化血管平滑肌层的肉碱棕榈酰基转移酶-1(CPT-1)表达影响。方法通过高胆固醇喂养建立兔动脉粥样硬化(AS)模型,设对照组(普通饲料,n=8)、高脂组(高胆固醇饲料,n=9)、辛伐他汀组(高胆固醇饲料加辛伐他汀,n=9),第9周和20周检测血清血脂水平,包括总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL);25周留取兔升主动脉、胸主动脉标本,病理形态学观察升主动脉组织学变化并进行病理形态学定量分析;RT-PCR测定胸主动脉血管平滑肌层CPT-1 mRNA的表达。结果高脂饮食诱导兔高胆固醇血症和动脉粥样硬化形成,外周血TC、TG、LDL升高,病理组织学显示内膜(I)中/层(M)厚度比值(I/M)、I M、内膜/中层面积比值(SI/SM)增大,动脉粥样硬化血管平滑肌层CPT-1表达下调;辛伐他汀组血脂水平明显降低(P<0.05),I/M、I M以及SI/SM明显减小(P<0.05),同时CPT-1 mRNA表达显著增强(P<0.05),与高脂组相比差异有显著性(P<0.05)。结论辛伐他汀早期应用可显著降低高胆固醇诱导的兔血脂水平,抑制动脉粥样硬化的形成,并显著增加血管平滑肌层CPT-1 mRNA的表达。     

吡格列酮对高脂饮食兔主动脉LOX-1表达的影响

目的探讨吡格列酮对高脂饮食下兔主动脉LOX-1表达的影响及其对动脉粥样硬化的作用。方法设立正常饮食、高脂饮食及高脂饮食加吡格列酮干预3组,通过比较主动脉病理形态学改变、血脂的变化、LOX-1分子及mRNA的表达进行研究,采用免疫组化检测兔主动脉LOX-1分子的表达,采用RT-PCR检测LOX-1mRNA的表达。结果吡格列酮能减轻高脂饮食所致的内膜增厚和平滑肌增生,减轻高脂血症所致动脉粥样硬化的发展。吡格列酮还能明显升高HDL,对TC、LDL、TG和BS无明显影响。高脂饮食刺激兔主动脉LOX-1分子及mRNA的表达,吡格列酮能显著减轻这种作用。结论吡格列酮能减轻高脂饮食兔主动脉LOX-1分子及mRNA的表达,这可能是噻唑烷酮类药物抗动脉粥样硬化的重要作用机制。     

固醇调节素结合蛋白调节辛伐他汀对血管平滑肌细胞的作用

目的 观察辛伐他汀对血管平滑肌细胞(VSMCs)是否存在双向作用,是否通过固醇调节素结合蛋白(SREBPs)调节起作用.方法 ①培养大鼠原代VSMCs,观察不同浓度辛伐他汀对VSMCs增殖、迁移的影响,以及SREBP-1、SREBP-2 mRNA在VSMCs的表达.②建立大鼠动脉粥样硬化血管损伤模型,分为动脉粥样硬化损伤组(n=6)、低剂量辛伐他汀组(n=6)和高剂量辛伐他汀组(n=6);另设正常对照(假手术)组(n=8).低剂量和高剂量辛伐他汀组每天1次灌胃给药,剂量分别为0.5 mg·kg-1·d-1和2.5 mg·kg-1·d-1,正常对照组和动脉粥样硬化损伤组喂予等量生理盐水,4周后处死动物.酶法测定各组血脂水平,检测胸主动脉和左颈总动脉内膜/(内膜+中膜)比值.RT-PCR法检测SREBP-1、SREBP-2 mRNA在血管的表达.结果 细胞及动物实验均证明辛伐他汀对VSMCs增殖和迁移无双向调节作用.低剂量辛伐他汀对VSMCs的增殖和迁移无促进作用,高剂量辛伐他汀抑制VSMCs增殖和迁移,且这种作用呈剂量依赖性但不依赖他汀的调脂性.辛伐他汀能激活VSMCs的SREBP-1、SREBP-2 mRNA表达,且高浓度辛伐他汀SREBP-1、SREBP-2 mRNA表达显著.结论 辛伐他汀可能通过激活SREBPs抑制血管平滑肌细胞增殖和迁移.     

辛伐他汀对高脂血症大鼠主动脉平滑肌细胞凋亡的影响

目的观察辛伐他汀对高脂血症大鼠主动脉平滑肌细胞凋亡的影响。方法采用高脂饲料喂养的方法建立高脂血症大鼠模型,将普通饲料喂养的SD大鼠设为正常对照组7只,成模大鼠随机分为高脂血症组10只及辛伐他汀组10只,药物干预4周后,处死大鼠取主动脉测定平滑肌细胞凋亡率。结果与高脂血症模型组比较,辛伐他汀组甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)均明显下降(P<0.05或P<0.01)。与高脂血症模型组比较,辛伐他汀组肝细胞脂肪变性的程度明显减轻。辛伐他汀组主动脉平滑肌细胞凋亡率为(34.8±1.86)%,高于高脂血症组主动脉平滑肌细胞凋亡率(27.1±1.37)%(P<0.01)。结论辛伐他汀能够降低高脂血症大鼠血脂,增加高脂血症大鼠平滑肌细胞凋亡率,延缓动脉粥样硬化的发生。     

基质金属蛋白酶-2及其组织抑制物-2在动脉粥样硬化兔主动脉中的表达变化

目的 研究基质金属蛋白酶-2(matrix metalloproteinase-2, MMP-2)及基质金属蛋白酶组织抑制物-2(tissue inhibitor of metalloproteinases-2, TIMP-2)在动脉粥样硬化兔主动脉组织中的表达及与血管病理改变的关系.方法 16只雄性新西兰兔随机分为对照组(喂食普通兔料)、高脂模型组(喂食高脂饲料),饲养12周后处死动物,取主动脉进行病理学检查, 并采用RT-PCR方法来检测主动脉病灶中MMP-2和TIMP-2 mRNA的表达.结果 MMP-2 mRNA在正常对照主动脉组织中低表达而在动脉粥样硬化病变时高表达;TIMP-2 mRNA在正常对照主动脉组织中高表达而在动脉粥样硬化病变时低表达.结论 MMP-2及TIMP-2的协同表达在动脉粥样硬化及动脉血管重塑过程中起作用,动脉粥样硬化的发生与两者的比例失调有关.     

Pentraxin3蛋白在兔动脉粥样硬化斑块中的表达研究

目的研究炎症因子正五聚素蛋白3(pentraxin 3,PTX3)在兔动脉粥样硬化斑块及正常动脉组织中的表达。方法 16只新西兰大白兔随机分为正常饮食对照组和高脂饮食组(每组8只),分别喂食普通饲料(100 g/d)和高脂饲料(100 g/d),持续16周。于实验第8周和第16周时,超声检查观察高脂饮食组主动脉粥样硬化斑块形成情况。于实验第16周,取高脂饮食组兔主动脉组织,苏丹Ⅲ染色观察主动脉粥样硬化情况。分别采用Real-Time PCR技术和Western blotting法测定高脂饮食组兔动脉粥样硬化斑块和正常饮食对照组兔正常动脉组织中PTX3 mRNA及蛋白表达。结果实验第16周,超声检查和组织学观察均证实高脂饮食组兔主动脉有粥样硬化斑块形成;高脂饮食组动脉粥样硬化斑块中PTX3 mRNA和蛋白的相对表达量均显著高于正常饮食对照组正常动脉组织,PTX3 mRNA表达分别为(2.815±0.531)和(1.022±0.175),PTX3蛋白表达分别为(0.470±0.056)和(0.248±0.053),差异均有统计学意义(P<0.01)。结论 PTX3在动脉粥样硬化斑块中的表达明显上调,是参与动脉粥样...     

辛伐他汀对家兔主动脉粥样硬化斑块血管内皮生长因子表达的影响

目的:观察辛伐他汀对动脉粥样硬化斑块血管内皮生长因子(VEGF)表达的影响.方法:雄性纯种新西兰大白兔,采用高脂肪、高胆固醇饲料喂饲构建主动脉粥样硬化(AS)模型,并随机分为辛伐他汀组(n=10)和单纯高脂饮食组(n=6);另有一组动物喂饲普通饲料作为空白对照组(n=8).采用免疫组织化学方法,观察3组动物AS斑块VEGF的表达情况.结果:辛伐他汀组和单纯高脂饮食组AS斑块VEGF阳性信号强度均显著高于空白对照组(P＜0.05);辛伐他汀组VEGF阳性信号强度又显著低于单纯高脂饮食组(P＜0.05).结论:提示辛伐他汀可一定程度稳定斑块,延缓AS的进程.     

拉西地平对动脉粥样硬化新西兰兔LOX-1的影响

目的：观察拉西地平对兔颈总动脉血凝素样氧化低密度脂蛋白受体-1（LOX-1）表达的影响。方法：球囊拉伤＋高脂饮食6周建立动物模型,将30只雄性新西兰白兔随机分成五组：Control组、M0del组、Laci—L组、Laci—H组和Atovas组。6周后检测血脂水平。计算左侧颈总动脉新生内膜面积（SI）与中膜面积（SM）之比（SI／SM）,病理形态学观察颈总动脉组织学变化,逆转录-聚合酶链反应（RT—PCR）和免疫组化分别检测颈总动脉血管壁LOX-lmRNA和蛋白的表达。结果：左侧颈总动脉球囊拉伤＋高脂饮食成功建立了兔动脉粥样硬化模型,在Model组中,血中总胆固醇（TC）、低密度脂蛋白（LDL-c）水平明显升高;SI／SM比值明显增大,颈总动脉血管壁LOX-lmRNA与蛋白水平表达增强;Laci—L组和Laci—H组血脂无明显降低,但是,SI／SM、LOX-lmRNA和蛋白水平较Model组显著降低（P〈0．01）。结论：拉西地平减少内膜LOX-1表达是其抗动脉粥样硬化作用机制之一。     

辛伐他汀对兔硬化髂动脉TNF-α的影响

目的研究辛伐他汀对兔粥样硬化髂动脉肿瘤坏死因子-α(TNF-α)表达的影响. 方法30只雄性新西兰大白兔,分别予普通饲料喂养(n=8)及高脂喂养(胆固醇1g/d,猪油10g/d;n=22)6周.高脂喂养2周后行髂动脉内膜球囊损伤术;术后辛伐他汀组(n=12)予辛伐他汀15mg/d;分组喂养4周后处死所有动物取一侧病变髂动脉做病理切片,用免疫组化方法观察TNF-α的表达情况;取另一侧病变髂动脉抽提总RNA和总蛋白,分别应用半定量逆转录多聚酶链式反应和Western蛋白印迹测定TNF-αmRNA和蛋白质水平的表达. 结果辛伐他汀可以显著降低兔血浆总胆固醇,降低粥样硬化髂动脉组织TNF-α的表达,正常对照组、基础对照组和辛伐他汀组动脉壁 TNF-α mRNA的相对值分别为0.16±0.024、0.56±0.050、0.37±0.031,相互间有统计学差异(P＜0.05),Western blot 检测和免疫组化结果一致. 结论辛伐他汀可以显著降低兔粥样硬化髂动脉组织TNF-α的表达.     

小剂量阿司匹林对动脉粥样硬化兔主动脉MMP-2表达的影响

目的评估小剂量阿司匹林对动脉粥样硬化兔主动脉基质金属蛋白酶-2(MMP-2)的表达及动脉硬化严重程度的影响。方法 24只雄性新西兰兔随机分为对照组(喂食普通兔料)、模型组(喂食高脂饲料)、阿司匹林组(喂食高脂饲料并给予小剂量阿司匹林干预),每组8只。饲养12周后处死动物,取主动脉进行病理学检查,分别应用RT-PCR和Western-bolt分析主动脉病灶中MMP-2 mRNA和蛋白的表达。结果病理学大体观察发现,对照组无动脉粥样硬化斑块形成,模型组和阿司匹林组主动脉斑块最大厚度、平均斑块厚度、管腔狭窄度和斑块所占周径比值等4项指标两两比较均有显著性差异(P<0.01)。对照组中MMP-2蛋白和mRNA呈低水平表达,而在模型组中的表达均明显增高,阿司匹林组MMP-2蛋白和mRNA的表达降低(P均<0.01)。结论 MMP-2在正常血管组织中低水平表达,随血管动脉粥样硬化程度的加重而升高;小剂量阿司匹林可以有效地减少动脉粥样硬化兔主动脉MMP-2表达,减轻动脉硬化的严重程度。     

Intervention of Tongxinluo Capsule (通心络胶囊) against Vascular Lesion of Atherosclerosis and Its Effect on Lectin-like Oxidized Low Density Lipoprotein Receptor-1 Expression in Rabbits

Lectin-like oxidized low-density lipoprotein(ox-LDL) receptor-1 (LOX-1) is a newly identifiedreceptor for cytotoxic ox-LDL in endothelial cellsand plays an i mportant role in the occurrence anddevelopment of atherosclerosis ( AS)(1). Clinicalstudies have showed that Tongxinluo capsule (通心络胶囊,TXL) could alleviate the symptoms of angi-na and myocardial ischemia in patients with coro-nary heart disease.But there werefewstudies con-cerning the effect or therapeutic mechanism of itspreve…     

Fluvastatin prevents renal injury and expression of lactin-like exidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia

Background Lipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery.Methods Twenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin ［10 mg·kg（-1）·d（-1）］ . After 16 weeks, serum total cholesterol (TC), low-density lipoprotein(LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using 99mTc-DTPA single photon emission computed tomograph (99mTc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry.Results High cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits. Conclusions Fuvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries.     

高脂饮食兔腹主动脉缩窄前后内膜平滑肌细胞和胶原平均光密度变化的研究

目的 研究动脉粥样硬化(AS)兔腹主动脉缩窄近端及远端内膜平滑肌细胞(SMCs)和胶原的变化.方法 将25只新西兰大白兔随机分为普通对照组、高脂手术组、高脂组,第8周和第28周检测总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL),28周后高脂手术组行腹主动脉缩窄术,其余组行假手术.32周后利用生物机能实验分析系统测量各组腹主动脉缩窄近端和远端的压力.行HE染色、苦味酸-天狼猩红染色及免疫组化方法分别观察腹主动脉形态学特征、胶原及SMCs.结果 ①高脂手术组缩窄近端内膜胶原较高脂组相同位置明显增多;高脂手术组缩窄远端内膜胶原较高脂组相同位置明显减少.②高脂手术组缩窄近端SMCs较高脂组相同位置增多,高脂手术组缩窄远端内膜SMCs 较高脂组相同位置减少.结论 AS兔腹主动脉缩窄近端血管内膜增厚,内膜胶原和SMCs增多;缩窄远端内膜变薄,内膜胶原和SMCs减少.     

Intervention of Tongxinluo capsule against vascular lesion of atherosclerosis and its effect on lectin-like oxidized low density lipoprotein receptor-1 expression in rabbits

Objective: To investigate the prevention by Tongxinluo capsule (TXL) of vascular lesions and its effect on the levels of protein and gene expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of vascular wall in rabbits with atherosclerosis (AS), and to explore its possible mechanism against AS.Methods: AS models were established by feeding New Zealand white rabbits with high-cholesterol diet, and 24 immature rabbits were randomly divided into the control group, model group and treated group (treated with TXL capsule). The indexes of total cholesterol (TO and low density lipoprotein (LDL) levels were measured at the 16th week. The intima thickness and the plaque area of abdominal aorta were quantitatively analyzed by pathological morphological analysis, the expression of macrophage and smooth muscle cell (SMC) in intima were detected by immunohistochemical method and histologic segments were stained by Hematoxilin-Eosin (HE) to identify the degree of atherosclerotic lesion in the model group and the prevention by TXL. The LOX-1 gene and protein expression in abdominal aorta was detected by semi-quantitative RT-PCR and immunohistochemistry, respectively.Results: In the model group, the levels of TC and LDL were significantly elevated, aortic intima thickened extensively, the intima area enhanced, and macrophages expression increased; the levels of LOX-1 gene and protein expression was up-regulated in endothelium and neo-intima of the abdominal aorta. The treatment with TXL reduced blood lipids, attenuated arterial intimai proliferation, markedly inhibited the expression of macrophage and excessively expressed the level of LOX-1.Conclusion: TXL has an inhibitory effect on blood lipids, and it can prevent the occurrence of vascular lesion and cure its development, and its protection against AS was possibly associated with a crucial endothelial protective action through lowering the expression of LOX-1 in vascular walls. Supported by the State Natural Science Foundation of China (No. 30371496).     

INHIBITORY EFFECT OF FLUVASTATIN ON AORTIC INTIMAL THICKENING IN NORMOCHOLESTEROLEMIC RABBITS

Objective, The anti-atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter-induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods. Fifty-six rabbits were randomly divided into eight groups( n = 7, each). Fluvastatin was given mixed with food at daily dose of 8mg/kg starting 5 days before catheterization. Light microscope, immanohistochemistry, transmis-sion electron microscope and RT-PCR assay were applied to assess vascular smooth muscle cell (VSMC) proliferation and apoptosis, as well as oncogene expression in vascular wall. Results. At day 10 and day 15 after catheter induced denudation intima/media( I/M) thickness ratio was obviously higher, and also the percentage of PCNA-positive cells and TUNEL-positive cells in media was significantly higher compared with controls. The intimal hyperplasia was mostly composed of α-SM-actin-pesitive cells. In rabbits given flu-vastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvas-tatin.The overexpression of proto-oncogene H-ras mRNA and decreased expression of anti-oncogene p53 mRNA were found after vascular injury, whereas fluvastatin significantly reduced H-ras mRNA and increased p53 mRNA expres-sion. Conclusion. Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated With the influence of fluvastatin on oncogene expression in the injured vascular Wall.     

咪达普利与缬沙坦对兔动脉粥样硬化相关因子表达的影响及意义

目的:研究咪达普利与缬沙坦对兔动脉中周期蛋白依赖激酶4(CDK4)、血管细胞黏附分子-1 (VCAM-1)、信号转导及转录活化因子3(STAT3)和P15mRNA量的表达影响,探讨其抗动脉粥样硬化的机制.方法:48只雄性大白兔随机分为4组,对照组、高脂饮食组(高脂组)、高脂饮食加咪达普利组(咪达普利组)和高脂饮食加缬沙坦组(缬沙坦组).喂养8周后处死兔子,测定各组血脂水平,并采用免疫组化法和RT-PCR法分别检测CDK4、VCAM-1、STAT3和P15mRNA量的表达.结果:高脂组、咪达普利组、缬沙坦组血清TC、TG、LDL-C水平均较对照组显著升高(均P＜0.01).咪达普利组和缬沙坦组内膜增生较高脂饮食组显著减轻(P＜0.01).CDK4、VCAM-1、STAT3在高脂组、咪达普利组和缬沙坦组中表达均较对照组显著增高(P＜0.01)；CDK4、VCAM-1、STAT3在咪达普利组和缬沙坦组中表达较高脂组显著减少(P＜0.01).P15mRNA表达在高脂组、咪达普利组和缬沙坦组均较对照组显著减少(P＜0.01),在咪达普利组和缬沙坦组表达均较高脂组显著增高(P＜0.01).结论:咪达普利与缬沙坦可明显抑制动脉粥样硬化的发生,其机制与阻断STAT3信号转导通路、抑制内膜细胞增殖有关.     

全反式维甲酸对兔颈动脉粥样硬化模型内膜增殖的影响

①目的观察全反式维甲酸（ATRA）对兔颈动脉粥样硬化模型内膜增殖的影响。②方法36只新西兰大白兔随机分为假手术组、对照组和ATRA治疗组;假手术组给予高脂饮食但手术不损伤颈动脉内膜,余操作同对照组;对照组给予高脂饮食加空气干燥损伤颈动脉内膜;ATRA治疗组在高脂饮食加空气干燥损伤颈动脉内膜的同时给予ATRA治疗,内膜损伤后1周和4周观察平滑肌细胞中增殖细胞核抗原（PCNA）和细胞周期素E（cyclin E）的表达及兔颈动脉内膜增殖的情况。③结果ATRA治疗组平滑肌细胞中的PCNA和cyclin E的表达较对照组明显减弱（F=7．65～8．89,q=4．27～10．33,P〈0．05、0．01）;颈总动脉病变也较对照组轻微（t=4．330～5．042,P〈0．01）。④结论ATRA能抑制兔颈动脉内膜损伤后内膜增殖,其机制可能为通过抑制cyclin E的表达而抑制平滑肌细胞的增殖。     

动脉粥样硬化病变中过氧化物酶体增殖激活受体γ的表达

目的：探讨动脉粥样硬化病变组织中过氧化物酶体增殖激活受体γ（PPARγ）的表达。方法：16只大耳白兔随机分为胆固醇饲料组和常规饲料组（对照组）,每组8只。胆固醇饲料组建立动脉粥样硬化模型,于饲养0、8和16周检测兔血清胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）,16周后取主动脉行组织形态学观察及PPARγ的免疫组织化学分析。结果：0周两组动物TC、TG、LDL差异无显著性（P>0.05）,胆固醇饲料组饲养8周及16周后血清TC、LDL较0周明显升高（P<0.01）,并且明显高于对照组（P<0.01） 。胆固醇饲料组动脉粥样硬化斑块形成,胆固醇饲料组和对照组斑块/内膜面积为(28.12±3.77)%和0（P<0.01）,内膜厚度为（67.47±7.13）μm和（4.45±0.58）μm（P<0.01）,内膜与中膜厚度比为0.878±0.370和0.054±0.007（P<0.01）;SP法、DAB染色,胆固醇饲料组和对照组PPARγ表达阳性染色百分比分别为（14.38±2.58）%和（7.82±0.96）%（P<0.01）。结论：动脉粥样硬化病变部位PPARγ过度表达,这种过度表达可能与动脉粥样硬化病变的发 生发展具有一定关系。     

Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits

Background Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet.Methods　Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS10.0.Results　The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6±13.7)% and (36.3±16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P&lt;0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group. Conclusion The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.