高胆固醇血症对家兔主动脉内皮依赖性舒张功能的影响及机制研究

目的探讨高胆固醇血症对动脉内皮依赖性舒张功能的影响及前列腺素类物质在其中的作用.方法新西兰兔40只,随机分为3组普通饮食组、高胆固醇组和阿司匹林组,观测离体胸主动脉乙酰胆碱(Ach)诱导的舒张反应及凝血烷A2[BF(血栓素A2,TXA2)和前列环素(PGI2)代谢产物-凝血烷B2(血栓素B2,TXB2)及6-酮-前列腺素F1α的生成.为观测TXA2受体拮抗剂SQ29548对动脉舒张功能的影响,将普通饮食组及高胆固醇组又各分为对照动脉和SQ29548动脉.结果高胆固醇组动脉Ach诱导的舒张功能较普通饮食组和阿司匹林组减弱,有显著性差异(P＜0.05);TXA2受体拮抗剂SQ29548显著改善高胆固醇组动脉Ach诱导的舒张功能障碍;Ach刺激状态下,高胆固醇组有内皮动脉TXB2的生成显著高于普通饮食组动脉,去内皮后这种差异丧失;高胆固醇组与普通饮食组动脉6-酮-前列腺素F1a的生成无显著差异.结论①高胆固醇血症引起的动脉舒张功能障碍与其增加内皮TXA2的生成有关.②小剂量阿司匹林可改善高胆固醇血症引起的内皮依赖性舒张功能异常.     

阿托伐他汀钙对原发性高胆固醇血症患者血管内皮细胞依赖性舒张功能的影响

目的 :研究阿托伐他汀钙对原发性高胆固醇血症 （HTC）患者血管内皮细胞依赖性舒张功能 （FMD）的影响。方法 :采用高分辨率超声技术 ,对 30例 HTC患者用阿托伐他汀钙治疗前后和 30例血浆胆固醇 （TC）水平正常的对照 （NC）组的血管 FMD进行检测。结果 :HTC组肱动脉 FMD较 NC组明显减弱 （3.4 %± 2 .6 % vs 13.8%± 3.8% ,P<0 .0 1） ,而两组对硝酸甘油反应的内皮非依赖性舒张功能 （NMD）无显著性差异 （P>0 .0 5 ）。 30例 HTC患者服用阿托伐他汀钙 10 mg治疗 12周后 ,TC从 6 .3± 0 .6 mm ol/ L降至 5 .0± 0 .5 mm ol/ L ,甘油三酯 （TG）从 1.8± 0 .4mm ol/ L降至 1.5± 0 .6 mmol/ L ,L DL - C从 4 .2± 0 .5 m mol/ L降至 3.0± 0 .6 mm ol/ L ,同时 FMD较治疗前显著改善 （11.6 %± 3.3% vs 3.4 %± 2 .6 % ,P<0 .0 1） ,而治疗前后肱动脉 NMD无显著性改变 （P>0 .0 5 ）。结论 :HTC患者存在 FMD障碍 ,经阿托伐他汀钙降胆固醇治疗后 ,受损的血管 FMD有明显改善     

洛伐他汀对临界和轻度高胆固醇血症患者的血管内皮舒张功能的影响

血管内皮功能失调是动脉粥样硬化病理过程中的早期改变.血浆胆固醇水平升高是动脉粥样硬化重要的独立危险因素.动物实验以及临床试验均显示高胆固醇血症患者在动脉粥样硬化斑块形成之前即可出现血管内皮功能失调,主要表现为内皮依赖舒张功能障碍.许多大规模的临床试验发现降胆固醇治疗能延缓动脉粥样硬化的进展和促进粥样斑块的消退,而且在短时间内出现显著的临床效益,远早于冠状动脉的病理形态学改变之前,因此推测降脂治疗对改善血管内皮功能有益[1,2].     

实验性高胆固醇血症与家兔腹主动脉粥样硬化的关系研究

目的　研究实验性高胆固醇血症与家兔腹主动脉粥样硬化的关系 ,评价胆固醇在家兔腹主动脉粥样硬化形成中的作用。方法　对 16只雄性家兔分别于高脂饲料喂饲前及 12周后进行腹主动脉超声检查 ,测量腹主动脉内膜 -中层厚度的最大值 (IMTm) ,测定血清总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL- c)、低密度脂蛋白胆固醇(L DL- c) ,计算 TC与 HDL- c之比 (C/ H) ,取腹主动脉做病理切片测量动脉 IMTm。结果　 12周后家兔腹主动脉IMTm值明显增高 ,TC、L DL - c、C/ H明显升高。 IMTm与 L DL - c及 C/ H呈正相关。 IMTm的超声与病理测值之间无显著性差异 ,并高度一致。结论　高胆固醇是动脉粥样硬化的重要危险因素 ,其中的 HDL- c及 L DL- c在总胆固醇中所占比例的变化与动脉粥样硬化病变的形成密切相关 ,超声方法检测活体家兔腹主动脉 IMT准确可行。     

高胆固醇血症对离体兔主动脉血管内皮依赖性舒张反应的影响

目的 :探讨高胆固醇血症对血管内皮依赖性舒张反应的影响。　　方法 :2 0只新西兰雄性兔随机分为两组 :正常对照组 (10只 )及高胆固醇血症组 (10只 )。4周后取出每只兔的降主动脉 ,5 mm宽的动脉环放置于含有 2 5 ml Kreb液的组织—器官水浴系统中。分别测量游离血管对乙酰胆碱 (10 - 1 0 ～ 10 - 5mol/ L )和腺苷 (10 - 1 0 ～ 10 - 4 mol/ L )的舒张反应变化 (% )。　　结果 :两组血胆固醇水平有显著差异 (正常对照组 0 .78± 0 .2 9mmol/ L ,高胆固醇血症组 2 5 .6 7± 2 .86 mmol/ L ,P<0 .0 1) ;高胆固醇血症组血管对乙酰胆碱舒张反应〔最大 (5 8.2± 6 .1) %〕与正常对照组〔最大 (10 3.2± 6 .9) %〕比较明显减弱 (P<0 .0 1) ;高胆固醇血症组血管对腺苷舒张反应〔最大 (4 5 .2± 13.0 ) %〕也较正常对照组〔最大 (10 3.2± 9.9) %〕减弱 (P<0 .0 1)。两组动脉组织学检查无动脉硬化的改变。　　结论 :高胆固醇血症降低血管内皮依赖性舒张反应 ;高胆固醇血症时血管内皮功能改变早于动脉粥样硬化的结构改变。     

高胆固醇血症及其治疗概念

现已证实,患冠心病的危险性随着血清胆固醇水平增加而递增。通过饮食疗法及/或药物疗法降低人群血清胆固醇水平,将会降低冠心病发病率和病死率。     

辛伐他汀对原发性高胆固醇血症患者内皮依赖性血管舒张功能的影响

目的观察原发性高胆固醇血症患者使用两种剂量辛伐他汀的疗效与安全性及对血管内皮功能的影响。方法60例原发性高胆固醇血症患者随机分为辛伐他汀10mg组(A组,10mg/d)与20mg组(B组,20mg/d),每组30例,均治疗8周,20例正常对照,不予治疗。分别于用药前及疗程结束后查血脂并用超声测定肱动脉内皮功能,同时观察用药安全性。结果(1)原发性高胆固醇血症患者肱动脉内皮依赖性舒张功能较对照组明显减弱(P<0.01)。(2)辛伐他汀10mg与20mg剂量均能有效降低高胆固醇血症患者血清总胆固醇(TC)及低密度脂蛋白胆固醇(LDL C)水平,并显著改善肱动脉内皮依赖性舒张功能,其中20mg剂量组疗效明显优于10mg剂量组。结论原发性高胆固醇血症患者血管内皮依赖性舒张功能受损,两种剂量辛伐他汀均能安全、有效地降低患者血清TC及LDL C并显著改善血管内皮依赖性舒张功能,辛伐他汀20mg剂量组的疗效明显优于10mg剂量组。     

他汀类药物对原发性高胆固醇血症患者血管内皮功能的影响

目的　观察辛伐他汀和氟伐他汀对原发性高胆固醇血症患者血管内皮功能的影响。方法　 6 0例原发性高胆固醇血症患者随机分为辛伐他汀组 (5mg/d)或氟伐他汀组 (2 0mg/d) ,每组 30例 ,均治疗 8周 ,2 0例正常对照。采用超声多普勒于治疗前后对其进行血管内皮功能的测定。结果　原发性高胆固醇血症患者肱动脉血流介导的舒张反应较对照组明显减弱 [辛伐他汀组 (3 38±5 48) % ,氟伐他汀组 (1 17± 5 15 ) % ,对照组 (17 5 8± 6 47) % ,P <0 0 0 1],而三组对硝酸甘油的反应差异无显著性 [分别为 (14 6 4± 6 6 8) % ,(14 46± 7 80 ) % ,(18 31± 6 84) % ,P >0 0 5 ]。辛伐他汀或氟伐他汀治疗 8周后均使血清总胆固醇和低密度脂蛋白胆固醇显著降低 ,同时肱动脉内皮依赖性舒张功能较治疗前亦有明显改善 [辛伐他汀组为 (14 6 8± 5 0 5 ) %比 (3 38± 5 48) % ,氟伐他汀组为(13 94± 6 6 8) %比 (1 17± 5 15 ) % ,P值均 <0 0 0 1],而治疗前后肱动脉对硝酸甘油的反应无显著性变化。结论　原发性高胆固醇血症患者血管内皮依赖性舒张功能受损 ,辛伐他汀或氟伐他汀治疗均可显著改善血管内皮依赖性舒张功能 ,二者之间差异无显著性。     

高胆固醇血症的现代认识

高胆固醇血症的现代认识成都市一医院心脑血管病研究室张廷杰吴桐当代医学面临的最大挑战在过去３０年中对动脉粥样硬化、冠心病（ＣＨＤ）的大量流行病学、实验及临床研究证实许多危险因素与之有关，其中最重要的有３个即：吸烟、高血压及高胆固醇血症。美国在６０年代开...     

冠心病与高胆固醇血症

什么是胆固醇？胆固醇是一种对人体正常功能具有重要作用的脂肪样物质。除部分从食物中摄取外，部分的胆固醇是由身体自行制造。     

Familial hypercholesterolemia supravalvular aortic stenosis and extensive atherosclerosis

Familial hypercholesterolemia is an autosomally dominant disorder caused by various mutations in low-density lipoprotein receptor genes. This can lead to premature coronary atherosclerosis and cardiac-related death. The symptoms are more severe in the homozygous type of the disease. Premature malignant atherogenesis leading to aortic root abnormalities causing supravalvular aortic stenosis is rare. Our case demonstrates the diagnostic imaging findings of the phenotype of patients who have severe elevated LDL with familial hypercolesterolemia.     

Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of short-term statin therapy in patients with hypercholesterolemia

The preventive effect of statins on coronary events is not only associated with the cholesterol-lowering effect of these drugs, but also various direct effects on the vascular wall, which include improvement of endothelial function, antioxidant activity, and anti-inflammatory activity. We investigated whether short-term statin therapy could improve arterial stiffness and assessed its mechanism of action in patients with hypercholesterolemia. We assessed arterial stiffness in 10 patients (mean age: 62.9 ± 9.0 years) with hypercholesterolemia (total cholesterol 220mg/dl). The patients were treated with cerivastatin (0.15mg/day) for 4 weeks. Before and after 4 weeks of treatment, we determined arterial stiffness from brachial-ankle pulse wave velocity and the ankle-brachial blood pressure index (ABI) using a FORM apparatus (Colin, Komaki, Japan). We also measured the blood levels of high-sensitivity C-reactive protein (hsCRP) and malondialdehyde low-density lipoprotein (MDA-LDL) as markers of inflammation and oxidation, respectively. After statin therapy, both the right and left abPWV were significantly decreased from 1544.6 ± 157.1 to 1349.0 ± 223.9cm/s and from 1592.1 ± 164.8 to 1424.8 ± 245.2cm/s, respectively (P < 0.05). However, the ABI was unchanged after 4 weeks of cerivastatin therapy. MDA-LDL decreased significantly (from 161.2 ± 42.4 to 119.4 ± 33.5U/l, P < 0.05) and hsCRP also decreased. Total cholesterol and LDL-cholesterol decreased, while triglycerides and high-density lipoprotein-cholesterol were unchanged. Blood pressure was not significantly altered from the baseline value by statin therapy. These results suggest that the preventive effect of statins on coronary events is partly associated with the various actions of these drugs on the vascular wall, and that statins are not only cholesterol-lowering agents but also antiatherosclerotic agents.     

阿托伐他汀对阿尔茨海默病并存高胆固醇血症患者的影响

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Effect of hypercholesterolemia on experimental colonic anastomotic wound healing in rats

AIM: To evaluate the mechanical and biochemical parameters of colonic anastomotic healing in hypercholesterolemic rats. METHODS: Sixty rats were divided into two groups of 30 each according to their dietary regimens. The test group was fed with a high cholesterol-containing diet for two months while the control group had standard diet. These two groups were further divided into three subgroups consisting of ten rats each. After hypercholesterolemia was established, left colon resection and anastomosis were performed in both groups and samples from liver and abdominal aorta were taken to evaluate the systemic effects of hypercholesterolemia. Anastomotic wound healing, blow-out pressures and tissue hydroxyproline levels were evaluated. RESULTS: The test group had a significant weight gain in two months. Microscopic examination of the abdominal aorta revealed no atherosclerotic change in none of the groups, but liver tissue specimens showed significant steatosis in the test group. Tissue hydroxyproline levels and anastomotic blow-out pressures were significantly lower in the test group than in the controls. CONCLUSION: Hypercholesterolemia not only increases hydroxyproline levels and blow-out pressures but also worsens anastomotic wound healing.     

家族性高胆固醇血症家系低密度脂蛋白受体活性及其基因突变分析

目的:对1例临床诊断为家族性高胆固醇血症(FH)纯合子患者家系进行低密度脂蛋白受体(LDL-R)活性研究及其基因突变分析,旨在探讨其分子病理机制。方法:对先证者及其父母进行血脂、颈动脉超声等检查;采用流式细胞仪检测先证者及其父母外周血淋巴细胞LDL-R表达量和功能;以先证者基因组DNA为模板,扩增载脂蛋白B100(ApoB100)基因3500区域片断,PCR产物进行核苷酸序列分析,排除由该突变导致家族性ApoB100缺陷症;用降落式PCR方法,在同一程序中分别扩增LDL-R基因的启动子和全部18个外显子片段,扩增产物进行核苷酸序列分析;发现突变后验证其父母是否存在相同基因突变。结果:先证者血清TC和LDL水平明显升高、颈动脉内中膜明显增厚;LDL-R的表达量和结合功能显著下降(分别为正常人的13.6%和21.1%);ApoB100基因3500区域未见突变,LDL-R基因第1864位碱基T取代了G发生纯合错义突变,导致第601位氨基酸天冬氨酸变成脯氨酸(D601Y)。其父母LDL-R基因发现了相同的杂合突变,经检索该突变在我国未见报道。结论:证实家系先证者存在LDL-R基因突变,分别来源于父系和母系的遗传,该突变可能是家系发病的分子基础;D601Y也可能是我国FH患者LDL-R基因一种新的突变类型。     

Effect of hyperlipidemic diets, proinflammatory agents and plasma expanders on leukocyte adhesion to the endothelium of aorta and carotid artery of rats

A comparative study of leukocyte adhesion to the endothelium of the thoracic aorta and left carotid artery in rats has been performed after administration of two hyperlipidemic diets for 15 days, proinflammatory agents (thrombin, lipopolysaccharide and zymosan activated serum) and plasma expanders [dextran, polyvinylpyrrolidone (PVP), rat albumin and several bovine albumins from different sources]. Leukocytes adhered to the endothelium were demonstrated in surface preparations by esterase activity. Activation of circulating leukocytes was measured by nitroblue tetrazolium reduction and luminol enhanced chemiluminescence. Both hyperlipidemic diets produced, in all rats, more leukocyte adhesion in the aorta than in the carotid artery. All proinflammatory agents produced at 1 h, increases in leukocyte adhesion — which in all rats were greater in the carotid artery than in the aorta — and leukocyte activation, which was higher at 3 h than at 1 h. Dextran, PVP, bovine albumins 103700 and A-4503 at 18 h produced slight increases in leukocyte adhesion in the aorta but not in the carotid artery. Rat albumin and bovine albumin A-7906 determined an intense determined and intense leukocyte adhesion at 18 h which was not preferential to either vessel. Adhesion produced by A-7906 was maximal at 12 h and partially inhibited by dexamethasone. The last albumin produced leukocyte activation at 3 h and was sequestered 5 min after administration, reaching normal values at 1 h. Albumins 103700 and A-4503 neither activated leukocytes nor were sequestered after administration.     

Cardio-ankle vascular index (CAVI) correlates with aortic stiffness in the thoracic aorta using ECG-gated multi-detector row computed tomography

Background

The cardio-ankle vascular index (CAVI) is an arterial stiffness index based on the stiffness parameter β, which is essentially independent of blood pressure. The objective of this study was to determine whether CAVI correlates with the regional stiffness parameter β and pulse wave velocity (PWV) in the thoracic aorta calculated from ECG-gated multi-detector row computed tomography (MDCT).

Methods and results

Forty-nine patients who underwent coronary MDCT for suspicious coronary artery disease were recruited. The largest and smallest vessel luminal cross-sectional areas of the thoracic aorta were measured from MDCT images to calculate PWV and stiffness parameter β of the ascending and descending aorta. CAVI was also measured by VaSera VS-1000.In univariate analysis, CAVI significantly correlated with regional stiffness parameter β and PWV, which was influenced by the inevitable part of the aging process in the ascending (r = 0.485, P < 0.001; r = 0.483, P < 0.001) and descending aortas (r = 0.304, P = 0.034; r = 0.327, P = 0.022), respectively. The regional stiffness parameter β did not correlate with systolic blood pressure (SBP), although the PWV correlated with SBP. In multivariate analysis, CAVI independently correlated with the stiffness parameter β, but not with the PWV.

Conclusion

These data suggest that CAVI, which correlated with stiffness parameter β in the thoracic aorta, has a potential role in evaluating integrated arterial stiffness including that of the central aorta.     

氟伐他丁治疗高胆固醇血症的疗效及对血清NO的影响

目的：观察氟伐他丁治疗高胆固醇血症的疗效及对血清一氧化氮（ＮＯ）的影响。方法：用硝酸还原酶比色法测定５０ 例高胆固醇血症和３５ 例正常对照组的ＮＯ。然后高胆固醇血症组口服氟伐他丁２０ ｍ ｇ,每晚１ 次,共８ 周,比较治疗前后的ＮＯ和血脂变化。结果：高胆固醇血症组氟伐他丁治疗前ＮＯ较对照组显著减低（ Ｐ＜ ０．０１）,经氟伐他丁治疗后ＮＯ较治疗前显著上升（ Ｐ＜０．０１）,治疗８ 周后血ＴＣ下降２２％ ,ＬＤＬ－Ｃ下降３０％ ,ＴＧ下降１２％ （均Ｐ＜ ０．０１）,ＨＤＬ－Ｃ上升８％ （Ｐ＜ ０．０５）。结论：氟伐他丁在降低胆固醇的同时,通过增加血管内皮ＮＯ的释放来改善内皮功能,从而有效地阻止动脉粥样硬化的发展。