糖尿病患者颈动脉粥样硬化多因素研究

目的 研究糖尿病患者颈动脉粥样硬化与血糖、血脂、凝血谱等多因素之间的关系。方法 对39例糖尿病患者行颈动脉超声检查，同时检测血糖、血脂、凝血谱等项目。34例非糖尿病患者作为对照组，两组的结果进行比较。结果 糖尿病组颈动脉粥样斑块发生率74．35％，对照组11．76％，差异有显著性（P〈0．01）。糖尿病组粥样斑块以颈总动脉分叉部位最多，占40％。糖尿病组血糖、胆固醇、载脂蛋白B、纤维蛋白原、高血压发生率与对照组比较差异有显著性（P〈0．05）。结论 糖尿病能促进颈动脉粥样硬化的形成，其形成还与脂质代谢紊乱、凝血谱异常、高血压等因素有关。     

Heritability of flow-mediated dilation: a twin study

BACKGROUND: Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic vascular disease and future cardiovascular events. OBJECTIVE: To estimate the heritability of brachial artery FMD using a twin design. METHODS: We estimated the heritability of FMD using 94 middle-aged male twin pairs. FMD was measured by ultrasound, and traditional coronary heart disease risk factors were measured. Genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in FMD. RESULTS: The mean age of the twin participants was 54.9 +/- 2.8 years. The mean FMD was 0.047 +/- 0.030. The intraclass correlation coefficient was higher in MZ twins [0.38, 95% confidence interval (CI) 0.32-0.43] than in DZ twins (0.19, 95% CI 0.11-0.26), suggesting a role of genetic influence in FMD variation. Structural equation modeling showed that both genetic and unique environmental factors contributed significantly to the variation in FMD. The crude FMD heritability was 0.37 (95% CI 0.15-0.54). After adjustment for traditional cardiovascular risk factors, including age, total cholesterol, blood pressure, and body mass index, the heritability of FMD was 39% (95% CI 0.18-0.56). The remaining variation in FMD could be explained by individual-specific environment. CONCLUSION: This is the first study using twins to estimate the relative contributions of genetics and environment to the variation in FMD in a US population. Our results demonstrate a moderate genetic effect on brachial artery FMD, independent of traditional coronary risk factors. Our data also highlight the importance of unique environment on the variability in FMD.     

载脂蛋白对无症状非糖尿病人群冠状动脉粥样硬化的预测价值

目的 分析无症状非糖尿病人群载脂蛋白(Apo)水平及ApoB/ApoA1比值,研究其与冠状动脉粥样硬化发生的相关性及对冠状动脉病变的预测价值。方法 回顾性分析2013年4月至2014年3月在中国人民解放军总医院行冠状动脉CT血管成像和血生化检查的无症状体检者401例,根据检查结果分为粥样硬化组(n=224)和对照组(n=177),比较两组相关危险因素、脂质及Apo水平,找出预测冠状动脉粥样硬化的最佳血脂指标。结果 粥样硬化组ApoB、ApoC2、ApoC3、ApoE水平及ApoB/ApoA1比值均显著高于对照组(P均＜0.01),ApoA1、ApoA2及脂蛋白a水平两组间差异无统计学意义(P均＞0.05)。Logistic回归分析结果显示,年龄、男性、高血压病史、ApoC3(OR=1.572,95%CI 1.200～2.061)及ApoB/ApoA1(OR=1.767,95%CI 1.335～2.338)是本研究人群冠状动脉粥样硬化的独立危险因素(P均＜0.01)。预测冠状动脉病变的受试者工作特征曲线分析结果显示,ApoB的曲线下面积最大,最佳截断点为1.005 g/L。结论 ApoC3与亚临床期冠状动脉粥样硬化关系密切,这一时期ApoA1降低并不明显,ApoB较其他脂类指标对无症状非糖尿病人群冠状动脉病变有很强的预测价值。     

CyPA 及 CD147在动脉粥样硬化兔血管重构中的表达

目的：探讨亲环素 A（CyPA）/ CD147在动脉粥样硬化（AS）兔血管重构中的表达特点。方法新西兰雄性白兔32只（3月龄）,随机分为对照组、模型组、液氮冻伤组、高脂饮食组（每组8只）。0周和13周分别检测兔血清 CD147和CyPA 表达水平。术后13周处死动物,取血管石蜡包埋切片,行 HE、弹力纤维染色,观察血管形态,并做巨噬细胞、CyPA、CD147免疫组织化学染色。利用计算机图像分析系统观察动脉损伤后血管重构相关指标的变化。结果13周时模型组、液氮冻伤组、高脂饮食组血 CyPA 与 CD147水平较同时期对照组均明显升高（P <0.05）,尤以模型组为甚。除对照组,其余3组均可见内膜增生,模型组还可见典型 AS斑块形成;斑块内及增生内膜均可见 CyPA 及 CD147的表达。模型组、液氮冻伤组、高脂饮食组最小管腔直径及管腔面积较对照组均明显减小（P <0.05）,内膜面积、中膜面积、最大内膜厚度、管腔狭窄度较对照组明显增大（P <0.05）。结论 CyPA 与 CD147在 AS 兔血管重构中的表达明显升高。     

颈动脉粥样硬化斑块MDCT定量分析

目的 探讨采用颈动脉粥样硬化斑块平扫CT值和强化幅度预测脑血管症状的价值。方法 纳入87例拟诊为颈动脉粥样硬化接受MDCT平扫及CTA的患者,根据有无脑血管症状分为有症状组(n=38)及无症状组(n=49),通过手动勾画ROI的方法测量CT平扫及CTA图像上斑块非钙化部分的CT值,采用独立样本t检验比较组间差异。应用ROC曲线分析采用平扫CT值及强化幅度判定是否引起脑血管症状的效能,并采用Z检验对曲线下面积进行比较。结果 有症状组和无症状组颈动脉斑块平扫CT值分别为(45.58±8.94)HU和(31.09±6.83)HU,二者差异有统计学意义(t=-8.569,P<0.001);有症状组颈动脉斑块强化增幅大于无症状组(t=-3.421,P=0.001)。ROC曲线阈值分析显示,平扫CT值最佳临界值为37.20 HU,判定是否引起脑血管症状的敏感度为92.10%(35/38),特异度为81.63%(40/49),准确率86.21%(75/87),ROC曲线下面积为0.937。强化幅度最佳临界值为10.1 HU,其敏感度为76.32%(29/38),特异度为63.27%(31/49),准确率为68.97%(60/87),曲线下面积为0.735;二者曲线下面积的差异有统计学意义(Z=3.613,P<0.01)。结论 颈动脉斑块非钙化部分平扫CT值和强化幅度与脑血管症状有关;斑块平扫CT值对判断是否引起脑血管症状的效能优于斑块强化幅度。     

急性脑梗死患者血清尿酸水平与颈动脉粥样硬化的关系研究

目的探讨脑梗死患者血清尿酸(uric acid,UA)水平与颈动脉粥样硬化(Carotid artery atherosclerosis,CAA)斑块及脑梗死的关系。方法检测78例脑梗死患者的血清尿酸(UA)、总胆固醇(total cholesterol,TC)、甘油三酯(Triglycerides,TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(Low-density lipoprotein,LDL-C)水平,并应用彩色多普勒超声检测其颈动脉内中膜厚度(intimal-medial wall thickness,IMT)及斑块。结果脑梗死组患者血清UA水平及IMT值高于对照组(P0.05),脑梗死组内高尿酸(HUA)组TG、LDL水平较尿酸正常组显著增加(P0.05)。脑梗死组内颈动脉粥样硬化亚组尿酸水平比较,IMT增厚组、斑块形成组尿酸水平较IMT正常组高(P0.05)。结论 HUA血症可能是脑梗死重要危险因素,且与颈动脉粥样硬化形成有关。     

Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate

One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.     

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low‐density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium‐dependent relaxations in cholesterol‐fed rats. For this purpose, rats were fed by 2% cholesterol‐enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium‐dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL‐cholesterol levels were found to be increased in cholesterol‐fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.     

米诺环素对5-LOX通路及动脉粥样硬化中炎症反应的抑制作用

目的米诺环素对5-LOX通路及动脉粥样硬化(atherosclorosis,AS)中炎症反应的抑制作用。方法以高脂喂养Apo E-/-小鼠建立AS模型,同时给予米诺环素或辛伐他汀治疗12周。比较各组小鼠的血脂水平,5-LOX的表达及其代谢物LTB4的含量;测定小鼠主动脉AS斑块的面积及斑块组成(脂质、胶原和巨噬细胞含量);PCR方法比较小鼠主动脉中相关炎症因子TNF-α、IL-6、VCAM-1、MMP-2、MMP-9 m RNA的含量。结果米诺环素能显著减少主动脉中5-LOX的表达及血液中LTB4的含量;降低小鼠主动脉中相关炎症因子TNF-α、IL-6、VCAM-1、MMP-2、MMP-9 m RNA的含量。在AS斑块的形成和发展中,米诺环素显著降低了Apo E-/-小鼠AS斑块的面积,减少斑块中巨噬细胞的含量并增加胶原的含量,提高斑块的稳定性。但是米诺环素没有改变Apo E-/-小鼠的血脂水平。结论米诺环素有抗AS的作用,其作用可能与其对5-LOX通路及炎性细胞和炎症介质的抑制作用有关。