硫酸乙酰肝素对家兔动脉粥样硬化的形成和脂蛋白代谢的影响

目的 探讨外源性硫酸乙酰肝素（HS）对形成中的动脉粥样硬化（AS）及其脂蛋白代谢的影响。方法 分离纯化HS，用以干预形成中的家兔实验性AS，酶法测定血清中各脂蛋白含量，制作石蜡，冰冻切片进行病理学检测，RT－PCR观察肝脏组织脂蛋白代谢相关受体的mRNA的表达。结果 HS降低血清总胆固醇和低密度脂蛋白－胆固醇含量，使高密度脂蛋白胆固醇与低密度脂蛋白胆固醇比值升高，加速动脉壁脂质沉积，促进AS的发展；促进肝脏对脂蛋白颗粒的蓄积，并增强低密度脂蛋白受体相关蛋白的mRNA表达。结论 外源性HS对AS形成及其脂蛋白代谢有重要的调节作用。     

四招助您“吃掉”胆固醇

胆固醇主要包括两种类型：高密度脂蛋白胆固醇（HDL—C）和低密度脂蛋白胆固醇（LDL—C）。LDL—C约占总胆固醇的60％．除一部分满足身体需要外，其他的会进入动脉血管内皮，形成斑块．阻塞血管．引起心脑血管疾病等；而HDL-C约占总胆固醇的30％，可以将多余的胆固醇转运出动脉内壁，送回肝脏进行代谢，它可以阻止动脉粥样硬化的发生。     

环氧合酶-2抑制剂对成核因子免疫球蛋白、黏蛋白作用的实验研究

胆囊结石是一种世界范围的常见病、多发病，其形成过程受到多种因素的影响，其中胆固醇结石的形成机制中可能包含有慢性炎症过程。塞来昔布(celecoxib)是新近研制的一种高选择性环氧合酶(COX)-2抑制剂，对胃肠道有较高的安全性。我们采用兔胆固醇结石模型，比较免疫球蛋白(Ig)、黏蛋白等与炎症有一定关系的成核因子含量的改变，探讨特异性COX-2抑制剂塞来昔布在胆固醇结石形成中的作用。     

实验性动脉粥样硬化海拔差异的超微结构研究

低、中和高海拔自然环境与动脉粥梗硬化关系的研究表明，随着海拔的升高，血清丙二醛、总胆固醇和甘油三酯下降，主动脉超微结构的损伤减轻，泡沫细胞形成减少，提示血清丙二醛，总胆固醇和甘油三酯的海拔性变化，可能是动脉粥样硬化海拔性差异形成的主要原因之一。     

刺玫果浸膏粉对动脉粥样硬化及胆固醇影响的实验研究

用高脂饲料喂饲鹌鹑，然后观察刺玫果浸膏粉对其血清总胆固醇含量及动脉壁粥样硬化斑块形成的影响。实验结果表明．刺玫果浸膏粉能显著降低鹌鹑血清总胆固醇的含量，减轻主动脉壁动脉粥样硬地斑块的形成。     

胆酸、小肠消化间期移行性复合波与胆固醇结石的关系

胆酸理化特性、代谢特性影响胆固醇结石形成。但同时在消化间期，胆酸肝肠循环作为结石形成的动力因素，可通过影响小肠消化间期移行性复合波(MMC)和胆囊运动，以脱氧胆酸为中介，促进致石胆汁形成，提高结石发生率。胆固醇结石胆囊切除术改变胆酸池体积、胆酸肝肠循环和小肠MMC。     

胆固醇性胆结石形成前胆囊前列腺素合成增加

胆汁中胆固醇的溶解度主要取决于胆盐、磷脂和胆固醇浓度,这对于阐明形成胆固醇性结石的生理生化基础有重要意义.但有资料表明,正常人胆汁中常可发现过饱和胆固醇而无胆结石及结晶.因此,过饱和胆固醇为胆结石形成所需要,但并非唯一的条件.核心形成物质有助于胆固醇性结石形成;若无结石核心,胆汁中过     

血脂康对实验性家兔动脉粥样硬化形成及其脂质过氧化损伤的影响

目的：探讨血脂康对实验性家兔动脉粥样硬化（ＡＳ）的形成及其脂质过氧化损伤的影响。方法：将纯种新西兰白兔采用随机分层分组法分为３组，即对照组、高脂组和治疗组。以高胆固醇饮食建立家兔动脉粥样硬化模型观察各组家兔血脂、血浆过氧化脂质、超氧化物歧化酶及主动脉、冠状动脉的病理改变。结果：血脂康能明显降低高胆固醇饮食家兔血清胆固醇、甘油三酯、低密度脂蛋白胆固醇含量（Ｐ＜０．０５），轻度增加血清高密度脂蛋白胆固醇含量（Ｐ＞０．０５），明显地抑制血浆过氧化脂质的形成（Ｐ＜０．０５）及超氧化物歧化酶含量的降低（Ｐ＜０．０５）；抑制肝脏、肾脏过氧化脂质的形成及超氧化物歧化酶含量的降低（Ｐ＜０．０５）。治疗组主动脉硬化斑块面积与动脉总面积比值明显降低，泡沫细胞层数明显减少，主动脉及冠状动脉病变明显减轻。结论：血脂康具有明显的调整血脂、抑制高胆固醇饮食家兔动脉粥样硬化形成及其脂质过氧化损伤的作用     

胆道胆固醇高分泌的形成机制

胆道胆固醇的过高分泌是胆囊胆固醇结石形成的主要病理生理改变。关于胆道胆固醇高分泌的确切病因目前尚不清楚，经研究与肝脏胆固醇代谢的多个不同环节有关。该综述将从肝脏胆固醇的合成、摄取、转化、酯化、转运以及分泌等方面对胆道胆固醇高分泌的发生机制进行阐述。     

高胆固醇饮食对胆结石形成的研究

通过高胆固醇饮食对胆结石形成的动物试验 ,探讨高胆固醇饮食的成石原因和机理 ,为在饮食上预防胆结石的形成提供试验依据 ,为胆结石的临床治疗和病人的康复提出理论依据 ,并为今后胆固醇结石的研究提供适宜的动物模型。本研究以狗作为试验动物 ,用 0 3%的高胆固醇饲料进行试验喂养 ,连续喂养 6周 ,观察动物胆结石的形成 ,测定血中胆固醇和甘油三酯水平 ,分析胆汁中成分的改变。在试验四周内试验组动物形成胆结石 ,且成石率为 10 0 % ,结石直径为 1mm～ 11mm。试验组动物血清胆固醇和甘油三酯水平显著提高 (p <0 0 1) ,胆汁中胆固醇和胆固醇结晶显著升高 (p <0 0 1)。通过高胆固醇膳食 ,试验动物血清及胆固醇和甘油三酯水平增加 ,胆汁中胆固醇增加 ,成石性胆汁形成。提示胆固醇代谢的异常变化在胆囊结石中起作用。     

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis

Little is known about the turnover rate (i.e. the rate of replication and death) of cells in the intima and media of human arteries as a function of age and atherosclerosis. One indicator of the replicative history of cells is telomere length. In this work we explored the rate of telomere attrition as a function of age and atherosclerosis in cells of the human abdominal aorta. Telomere length, measured by the terminal restriction fragment using Southern analysis, was determined in the intima and media of the distal (infrarenal) versus proximal (suprarenal) segments of the abdominal aorta. Telomere length was then correlated with age and atherosclerotic grade. The rate of age-dependent telomere attrition was higher in both the intima and media of the distal versus proximal abdominal aorta. In addition, telomere length was negatively correlated with atherosclerotic grade. However, after adjustment for age, this relationship was not statistically significant. The high rate of age-dependent telomere attrition in the distal abdominal aorta probably reflects enhanced cellular turnover rate due to local factors such as an increase in shear wall stress in this vascular segment.     

Complete atherosclerosis regression after human ApoE gene transfer in ApoE-deficient/nude mice

The apolipoprotein E (apoE)-deficient mouse is a relevant animal model of human atherosclerosis. Although the prevention of atherosclerosis development has been documented after somatic gene transfer into animal models, regression of lesions remains to be demonstrated. Thus, we used this genetically defined mouse model nn the nude background to show atherosclerosis regression. ApoE-deficient nude mice were infected with 5 x 10(8) or 10(9) plaque-forming units of a first-generation adenovirus encoding human apoE cDNA. The secretion of human apoE resulted in a rapid decrease of total cholesterol, which normalized the hypercholesterolemic phenotype within 14 days (from 600+/-100 to <100 microg/mL). Transgene expression was observed during a period of >4 months, with a normalization of cholesterol and triglyceride levels during 5 months. At that time, we successfully reinjected the recombinant adenovirus and observed the appearance of the human protein as well as the correction of lipoprotein phenotype. In mice killed 6 months-after the first infection, we observed a dose-dependent regression of fatty streak lesions in the aorta. We showed sustained expression of a transgene with a first-generation adenoviral vector and a correction of dyslipoproteinemia phenotype leading to lesion regression. These data demonstrate that somatic gene transfer can induce plaque regression.     

Combined effects of cholesterol reduction and apolipoprotein A-I expression on atherosclerosis in LDL receptor deficient mice

Reduction of total and LDL cholesterol reduces atherosclerosis and clinical cardiovascular events. High density lipoprotein (HDL) cholesterol levels have a strong inverse association with atherosclerosis, and overexpression of apolipoprotein A-I (apoA-I), the major protein component of HDL, reduces atherosclerosis in hypercholesterolemic animals. However, little is known about the potential for additive or synergistic effects between cholesterol reduction and apoA-I overexpression on atherosclerosis. In the current study, we tested the hypothesis that significant reduction of plasma cholesterol combined with overexpression of apoA-I would reduce atherosclerosis to a greater extent than either one alone. We used somatic gene transfer of the LDL receptor (to induce cholesterol reduction) and apoA-I in LDL receptor deficient mice fed a Western type diet and compared the combination to expression of each gene alone and to controls. Atherosclerosis was quantitated using two independent methods, by en face analysis of the entire aorta and by cross-sectional analysis of the aortic root. Although the reduction of cholesterol was transient, expression of the LDL receptor alone significantly reduced atherosclerosis by 45% in the aorta and 44% in the aortic root compared with controls. Overexpression of human apoA-I alone reduced atherosclerosis by 42% in the aorta and 44% in the aortic root compared with controls. Co-expression of the LDL receptor with apoA-I resulted in significantly higher levels of apoA-I than expression of apoA-I alone. Although co-expression of the LDL receptor and apoA-I reduced atherosclerosis by 37% in the aorta and 32% in the aortic root compared with controls, the reduction in atherosclerosis was no different than that seen with expression of the LDL receptor alone or apoA-I alone. In summary, in this relatively short-term murine model, simultaneous reduction of cholesterol and expression of apoA-I was associated with higher levels of apoA-I than expression of apoA-I alone but did not result in greater reduction in atherosclerosis compared with either one alone.     

Aortic Distensibility and Aortic Intima‐Media Thickness in Patients without Clinical Manifestation of Atherosclerotic Cardiovascular Disease

Background: There is growing evidence that aortic distensibility (AD) is a subclinical marker of early atherosclerosis. Aortic intima‐media thickness (IMT) was an earlier marker than carotid IMT of preclinical atherosclerosis. In this study, we aimed to assess the relationship between thoracic aortic IMT and AD. Methods: We studied 192 patients (mean age: 45.5 ± 8.4 years) who underwent transesophageal echocardiography (TEE) for various indications. Four different grades were determined according to IMT of thoracic aorta (Grade 1 < 1 mm; 1 mm ≤ Grade 2 < 3 mm; 3 mm ≤ Grade 3 < 5 mm; 5 mm ≤ Grade 4). AD was calculated from the echocardiographically derived ascending aorta diameters and hemodynamic pressure measurements in all patients. High sensitive C‐reactive protein (hsCRP) and other biochemical markers were measured using an automated chemistry analyzer. Results: TEE evaluation characterized thoracic aortic intimal morphology as grade 1 in 71 patients (37%), grade 2 in 57 patients (29.7%), grade 3 in 34 patients (17.7%), and grade 4 in 30 (15.6%) patients. The lowest AD level was observed in grade 4 group compared with grade 1 and grade 2 groups (P < 0.001, P = 0.009, respectively). AD level of grade 3 group was lower than grade 1 and grade 2 group (P < 0.001, P = 0.021, respectively). In multiple linear regression analysis, AD was independently associated with age (β = ?0.138, P = 0.029), hsCRP (β = ?0.209, P = 0.001), and aortic IMT (β = ?0.432, P < 0.001). Conclusion: AD is independently associated with age, thoracic aortic IMT, and hsCRP. Impaired elasticity index of the aorta might be an independent predictor for the severity of thoracic atherosclerosis.     

Measurement of atherosclerotic plaque volume in hyperlipidemic rabbit aorta by intravascular ultrasound

OBJECTIVES: Atherosclerotic changes in the rabbit have been evaluated by various methods. Although most previous studies have analyzed atherosclerotic plaque in the femoral, carotid and iliac arteries of rabbits by intravascular ultrasound (IVUS) because of easier access, we established a method for the precise measurement of plaque volume as well as plaque area in the thoracic descending aorta in the Watanabe heritable hyperlipidemic (WHHL) rabbit, which has severe atherosclerosis. METHODS: WHHL and Japanese White (JW)rabbits were used. An IVUS catheter was inserted into the right femoral artery and advanced to the left subclavian artery, which was used as an anatomical landmark. After IVUS image acquisition, the catheter was removed. Vessel volume, lumen volume and plaque volume were analyzed. RESULTS: Atheroma of the aorta was easily detected in WHHL rabbits by IVUS examination, whereas atherosclerosis was not observed in JW rabbits. The atheroma showed a low-echoic lesion compared to the adventitia, with morphological characteristics similar to human lipid-rich, soft atheromatous plaques. In 15-month-old WHHL rabbits, the vessel volume, lumen volume and plaque volume in the thoracic descending aorta were 815 +/- 109, 559 +/- 107 and 256 +/- 10 mm3/ 3 cm, respectively. CONCLUSIONS: We established a method for the precise quantitation of plaque volume by IVUS technology in WHHL rabbits aorta for the first time. This method is useful for evaluating several locally or generally delivered therapeutic agents in a hyperlipidemic animal model.     

丹参对实验性动脉粥样硬化形成的预防

目的:探讨丹参抑制动脉粥样硬化(AS)作用中的可能的分子机制。方法:随机将21只家兔均分为 对照组、AS组和丹参干预组,采用高脂饲料建立AS模型,9周后行血脂测定、主动脉粥样斑块面积计算,并以逆 转录 聚合酶链式反应(RT PCR)分别进行三组的单核细胞趋化蛋白 1(MCP 1)mRNA表达水平测定,以及用免 疫组织化学方法对比各组MCP 1蛋白表达。结果:对照组和丹参组中血脂水平和主动脉粥样斑块面积低于AS 组(P<0.01);主动脉血管内皮细胞以及平滑肌细胞内MCP 1mRNA水平及蛋白表达水平在对照组和丹参组中 明显低于AS组(P<0.01)。结论:丹参能降低MCP 1表达水平,这可能是其抑制AS形成的分子学机制之一。     

实验性兔动脉粥样硬化发病过程中内源性一氧化碳及其合成酶基因表达的改变

为研究内源性一氧化碳及其合成酶血红素氧化酶１在动脉粥样硬化发病中的变化规律，通过逆转录－聚合酶链反应、原位杂交、免疫组织化学染色和生物化学等多项指标观察血红素氧化酶１和内源性一氧化碳在动脉粥样硬化发病过程中的变化。结果发现，血红素氧化酶１ｍＲＮＡ主要分布于主动脉和冠状动脉内皮细胞，在动脉粥样硬化的发展过程中其表达有逐渐增高的趋势，且血红素氧化酶１蛋白的表达也有逐渐增高的趋势。血红素氧化酶１免疫组织化学染色显示，主动脉和冠状动脉内皮细胞呈阳性，主动脉壁血红素氧化酶１ｍＲＮＡ的表达量及血红素氧化酶活性和内源性一氧化碳的浓度有逐渐增高的趋势。结果提示，内源性一氧化碳及其合成酶在动脉粥样硬化的发病过程中可能具有重要的作用。     

3beta-Hydroxysteroid dehydrogenase in human aorta

3beta-Hydroxysteroid dehydrogenase (3beta-HSD) is known to be involved in steroid production and/or metabolism and to be expressed in many tissues including adrenal cortex. Expression of this enzyme has also been elucidated in human cardiovascular system but its details remain largely unknown. Therefore, in this study, we examined the status of 3beta-HSD in postmortem human aorta utilizing RT-PCR and immunohistochemical analysis. Both mRNAs and immunoreactivity for the enzyme were detected predominantly in female aorta, and in those with mild atherosclerotic changes. In addition, immunohistochemical study demonstrated that immunoreactivity for 3beta-HSD was detected in vascular smooth muscle cells (VSMCs) of aorta. These findings all indicated that steroidogenesis via 3beta-HSD may occur in VSMCs of human aorta, possibly related to gender differences and/or the degree of atherosclerosis.     

一种大鼠动脉粥样硬化斑块模型的建立

目的试建立一种大鼠动脉粥样硬化斑块模型。方法给予大鼠一次维生素D33×105U/kg体重肌肉注射、球囊损伤主动脉内皮和饲以含2％胆固醇、0.5％胆酸钠、0.2％丙硫氧嘧啶、3％猪油和维生素D31.25×106U/kg的高脂饲料90 d。结果90 d后大鼠血脂明显增高,胸主动脉形成明显的动脉粥样硬化斑块,斑块内有大量的泡沫细胞、脂质、巨噬细胞及钙化,中膜平滑肌明显萎缩;而仅饲以高脂饲料的大鼠胸主动脉结构未见改变。结论血管钙超载、内皮损伤和高脂可使大鼠主动脉形成较典型的动脉粥样硬化斑块。