HDL功能检测与冠状动脉斑块的相关性

目的针对正常高密度脂蛋白胆固醇(HDLC)水平(≥1.03 mmol/L)的冠心病患者,分析其血浆高密度脂蛋白(HDL)功能与冠状动脉狭窄及斑块性质的相关性。方法选取2015年10月至2017年12月在宜昌市中医医院接受64排螺旋CT冠状动脉造影(CTA)检查,并具有正常HDLC水平的疑似冠心病患者129例为研究对象,利用CTA检测进行冠状动脉狭窄程度及斑块性质分组,统计分析血浆HDL功能指标对氧磷酶1(PON1)活性及HDL氧化/抗氧化指数与其相关性。结果与非冠心病组比较,冠心病组HDLC水平、PON1活性下降,HDL氧化/抗氧化指数升高,显示为氧化状态,而ApoAI水平没有差异。随着冠状动脉狭窄程度增加,PON1活性逐渐降低,HDL氧化/抗氧化指数逐渐增高,而HDLC水平、ApoAI水平无明显差异。不同斑块性质分组分析显示,钙化斑块组PON1活性高于软斑块组及混合斑块组。PON1活性与HDLC、HDL氧化/抗氧化指数有一定相关性。结论HDL的功能检测中PON1活性对于冠心病的斑块性质及狭窄程度有良好的评价价值。     

肥胖伴糖耐量异常者经吡格列酮治疗后血清脂蛋白亚类的变化

目的　研究肥胖伴糖耐量异常者血高密度脂蛋白（HDL）亚类分布情况以及吡格列酮干预后对血浆HDL亚类分布的影响。方法　比较40例健康人与40例肥胖伴糖耐量异常者血浆高密度脂蛋白（HDL）亚类分布,了解肥胖伴糖耐量异常者血浆HDL亚类分布特点。采用配对设计的随机分组方法,以性别作为随机配对的条件,将40例肥胖伴糖耐量异常者作为研究对象分为安慰剂组和吡格列酮组,药物干预12周后,抽取受试者空腹12　h静脉血,24　h内进行HDL各亚组分含量的测定以及对氧磷酶1（PON-1）活性的测定。分析血浆HDL亚类分布与PON-1活性的相关性。结果　肥胖伴糖耐量异常者血清HDL分布异常,HDL2a和HDL2b减低,而小颗粒的preβ1-HDL、preβ2-HDL、HDL3a升高,差异具有统计学意义（P<0.05）。与安慰剂组比较,吡格列酮组用药后12周,受试者血清HDL中HDL2a、HDL2b、PON-1显著升高,preβ1-HDL显著降低,差异具有统计学意义（P<0.05）。相关性分析显示,preβ1-HDL与PON-1呈负相关,　HDL2b与PON-1呈正相关,相关性有显著性。结论　肥胖伴糖耐量异常患者血清中HDL亚类分布异常,成熟代谢过程受阻,趋向于较弱的抗动脉粥样硬化的分布趋势。吡格列酮通过改善HDL亚类的分布以及提高PON-1活性,增强了HDL抗动脉粥样硬化的作用。HDL亚类分布中成熟的大颗粒含量越高,PON-1的活性越强,抗动脉粥样硬化能力越强。     

酶育牛黄对血脂异常小鼠高密度脂蛋白功能的改善作用

目的探讨酶育牛黄(CBCG)对高脂食物诱导的血脂异常小鼠高密度脂蛋白(HDL)功能的影响。方法7~8周龄雄性C57BL/6J小鼠41只,随机分三组:对照组(溶媒组,n=14)、CBCG高剂量组[2.25 g/(kg·d),n=14]、CBCG中剂量组[0.75 g/(kg·d),n=13]。高脂(15.8%)高胆固醇(1.25%)饮食,自由饮水。连续灌胃12周后,禁食12 h,麻醉,小鼠内眦静脉取血,通过超速离心法获得低密度脂蛋白(LDL)、高密度脂蛋白(HDL)。通过胆固醇逆向转运(RCT)功能实验检测HDL对巨噬细胞源性泡沫细胞的胆固醇溢出的影响;通过HDL对Cu2+诱导的LDL氧化程度的保护作用,检测HDL的抗氧化功能;通过MTT比色法检测内皮细胞存活率,检测HDL抗内皮细胞凋亡功能;通过单核细胞黏附实验检测HDL抗炎功能。另外,40只7~8周龄雄性Apo E-/-小鼠随机分为四组:对照组(溶媒组,n=10)、CBCG低、中及高剂量组[0.25 g/(kg·d)、0.75 g/(kg·d)、2.25 g/(kg·d),n=10]。给予高脂(15.8%)高胆固醇(1.25%)饮食,自由饮水。连续灌胃8周末,禁食12 h,麻醉,小鼠内眦静脉取血,取材。ELISA检测血浆炎症因子白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平,分光光度计法检测血浆丙二醛(MDA)和对氧磷酶1(PON-1)水平;ELISA测定CBCG血浆活性成分胆红素和牛磺酸水平;酶法测定血浆总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)水平。结果 CBCG可显著改善C57BL/6J小鼠血浆HDL功能,主要表现在促进巨噬细胞内3H标记胆固醇的溢出;抑制Cu2+诱导的LDL氧化作用;抑制单核细胞黏附作用和改善内皮细胞保护作用。另外,血浆IL-6和TNF-α水平显著降低;血浆氧化生物指标MDA显著降低,PON-1显著升高;CBCG高剂量组血浆胆红素水平显著高于对照组,血浆牛磺酸水平呈升高趋势,但差异无统计学意义。CBCG治疗组TC和非高密度脂蛋白胆固醇(non-HDLC)水平变化无统计学意义,HDLC水平显著升高。结论 CBCG能改善C57BL/6J小鼠HDL功能,包括促进胆固醇溢出、抗氧化、抗凋亡、抗黏附和内皮保护作用。这种对HDL功能的改善作用可能与CBCG的血浆抗氧化作用有关。     

代谢综合征患者白细胞介素6水平与HDL亚类分布的相关性分析

目的探究代谢综合征(MS)患者血浆白细胞介素6(IL-6)水平与高密度脂蛋白(HDL)亚类分布及其相关性。方法收集MS组患者135例和对照组健康体检人群77例的血样,酶联免疫吸附法(ELISA)测定IL-6含量,按IL-6浓度将MS患者分为低IL-6组(IL-6≤66.76 ng/L)、中IL-6组(66.76 ng/LIL-6113.84 ng/L)、高IL-6组(IL-6≥113.84 ng/L)。双向电泳-免疫印迹法测定血浆HDL亚类的相对含量,全自动生化分析仪测定血脂浓度及载脂蛋白含量。分析不同性别对IL-6、血脂、载脂蛋白及HDL亚类分布的影响,及IL-6水平与HDL亚类分布的相关性。结果与对照组比较,MS组IL-6、preβ1-HDL、HDL3b、HDL3c、TC、TG、LDLC含量以及LDLC/HDLC和Apo B100/Apo AI均显著增高(P0.05或P0.01),而HDL2a、HDL2b、preβ2-HDL、Apo AI和HDLC含量显著降低(P0.05或P0.01)。与对照组同性别比较,MS组男性或女性HDL亚类的相对含量有差异(P0.05或P0.01);与同组男性比较,对照组和MS组女性血脂、血浆载脂蛋白水平差异均无统计学意义(P0.05)。MS患者血浆IL-6含量的升高与HDL亚类分布异常存在相关性,即IL-6的含量与小颗粒的preβ1-HDL、HDL3b水平呈正相关,与大颗粒HDL2b水平呈负相关。结论 MS患者血浆IL-6水平升高,且HDL颗粒呈变小趋势,高水平的IL-6可能与HDL亚类分布异常和血脂紊乱有关。     

代谢综合征患者血浆网膜素1水平与HDL亚类分布的相关性分析

目的探讨代谢综合征(MS)患者血浆网膜素1(Omentin-1)水平对高密度脂蛋白(HDL)亚类分布的影响。方法收集在南华大学附属医院就诊的MS患者102例和对照组81例的血样,采用全自动生化分析仪测定血脂浓度及载脂蛋白含量,酶联免疫吸附法测定Omentin-1的含量,双向电泳-免疫印迹法测定人血浆HDL亚类的相对含量。按Omentin-1浓度均值加减去一个标准差作为分割点,将MS患者分为3组:低Omentin-1组(Omentin-1≤9.10μg/L)、中Omentin-1组(9.10μg/LOmentin-126.68μg/L)、高Omentin-1组(Omentin-1≥26.68μg/L)。结果随着Omentin-1浓度的降低,MS患者血浆甘油三酯(TG)、总胆固醇(TC)及ApoB100/AⅠ和LDLC/HDLC比值均显著性增高(P0.05或P0.01),高密度脂蛋白胆固醇(HDLC)、ApoAⅠ含量显著降低(P0.05或P0.01)。与低Omentin-1组相比,高Omentin-1组中小颗粒的preβ1-HDL和HDL3b含量显著下降(P0.05或P0.01),而大颗粒的HDL2a含量显著上升(P0.05)。结论 MS患者血浆Omentin-1水平降低,且HDL颗粒呈变小趋势,低水平的Omentin-1可能与HDL亚类分布异常和血脂紊乱有关。     

代谢综合征患者血浆甘油三酯水平对HDL亚类分布的影响

目的探讨代谢综合征(MS)患者血浆甘油三酯(TG)水平对高密度脂蛋白(HDL)亚类分布的影响。方法选取在南华大学附属第一医院就诊的MS患者血样,全自动生化分析仪测定血脂含量及载脂蛋白浓度,根据美国国家胆固醇教育计划NCEP ATP-Ⅲ文件,将MS患者按TG浓度分4组,即TG1.69 mmol/L、1.69mmol/L≤TG2.25 mmol/L、2.25 mmol/L≤TG5.64 mmol/L、TG≥5.64 mmol/L,采用双向电泳-免疫印迹检测法测定MS患者和99例正常人血浆HDL亚类的相对含量。结果与对照组相比,MS患者血浆总胆固醇(TC)、TG、低密度脂蛋白胆固醇(LDLC)、载脂蛋白B100(Apo B100)、preβ1-HDL、HDL3b含量及Apo B100/AⅠ和LDLC/HDLC比值均显著性增高(P0.05或P0.001),HDLC、Apo AⅠ、HDL2b、HDL2a显著降低(P0.05或P0.001)。并且随着血浆TG水平的升高,小颗粒的preβ1-HDL、HDL3a和HDL3b含量升高,而大颗粒的HDL2b和HDL2a含量降低。结论MS患者HDL亚类分布异常,小颗粒的preβ1-HDL和HDL3b含量升高,而大颗粒的HDL2b和HDL2a含量降低,血浆TG含量变化可能是影响MS患者HDL亚类异常的因素之一。     

冠心病患者血浆微小RNA作为生物标记物可能性的研究

目的探讨微小RNA(miRNA)在动脉粥样硬化性心脏病患者循环血浆中表达特点。方法选择男性冠心病患者32例作为冠心病组,男性健康体检者20例作为对照组。另选择载脂蛋白(apo)E-/-小鼠10只为实验组,正常C57BL/6J小鼠10只为观察组,用高通量基因芯片技术分析实验组和观察组小鼠血浆中差异表达的miRNA。用实时定量PCR法检测冠心病组和对照组miRNA的表达。结果与观察组比较,实验组小鼠血浆有14种miRNA显著差异表达,其中6种显著上调3.02~3.46倍,8种显著下调3.02~4.21倍。与对照组血浆miRNA表达比较,冠心病组miR-34a和miR-21显著上调、miR-23a显著下调(P<0.01)。结论冠心病患者循环血浆中miR-23a、miR-21、miR-34a较健康人群明显升高,提示这3种miRNA具有成为冠心病患者生物标记物的潜能。     

高密度脂蛋白颗粒大小与青年冠心病无症状性心肌缺血的关系

目的 探讨高密度脂蛋白(HDL)颗粒大小与青年冠心病无症状性心肌缺血(SMI)的相关性。方法 共纳入469例青年冠心病患者,其中无症状性心肌缺血组194例(SMI组,n=194),有症状性心肌缺血组275例(non-SMI组,n=275)。收集患者的一般资料,检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)、载脂蛋白A1(ApoA1)水平及相关生化指标。计算HDL颗粒大小的量化指标HDLC/ApoA1,以及相关脂质参数TC/HDLC、non-HDLC、TG/HDLC、LDLC/HDLC。应用多因素Logistic回归分析明确HDL颗粒大小(HDLC/ApoA1)与青年冠心病SMI发生的关系。结果 与non-SMI组比较,SMI组患者血清TC、尿酸、LDLC、LDLC/HDLC、TC/HDLC、non-HDL水平偏低,HDLC、ApoA1、HDLC/ApoA1值更大(均P＜0.05)。相关分析结果显示,HDL颗粒大小(HDLC/ApoA1)与Gensini积分呈负相关(r=－0.405,P＜0.05)。多因素分析显示,HDL颗粒大小(HDLC/ApoA1)是青年冠心病患者SMI的独立预测因子(OR=0.697,95%CI:0.233~0.910,P=0.007)。受试者工作特征曲线显示,以0.36为HDL颗粒大小(HDLC/ApoA1)临界值预测青年冠心病SMI发生的灵敏度为92.1%,特异度为75.5%。结论 HDL颗粒大小(HDLC/ApoA1)与青年冠心病SMI患者冠状动脉病变严重程度呈负相关,对青年冠心病SMI具有较强的预测价值。     

血浆胆固醇含量对代谢综合征患者HDL亚类分布的影响

目的探讨代谢综合征(MS)患者血浆胆固醇水平对高密度脂蛋白(HDL)亚类分布的影响。方法采用全自动生化分析仪测定MS患者血浆血脂含量及载脂蛋白浓度,用双向电泳-免疫印记法测定血浆HDL亚类的含量。并根据中国成人血脂异常防治指南,将MS患者按血浆总胆固醇(TC)浓度分为3组,即TC正常范围组:TC5.17 mmol/L、TC临界升高组:5.17 mmol/L≤TC6.21 mmol/L、TC升高组:TC≥6.21 mmol/L。结果与对照组相比,MS患者血浆空腹血糖(FPG)、TC、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、载脂蛋白B100(apo B100)、preβ1-HDL、HDL3b含量及apo B100/AI和LDLC/HDLC比值均显著性增高(P0.05或P0.001),HDLC、apo AI、HDL2a、HDL2b显著降低(P0.05或P0.001);并且随着血浆TC水平的升高,小颗粒的preβ1-HDL和HDL3b含量升高,而大颗粒的HDL2a和HDL2b含量降低。MS患者HDLC的含量降低和(或)LDLC含量升高都存在不同程度的血浆HDL亚类分布异常,而且HDLC含量异常时存在HDL各亚类分布异常的程度较LDLC含量异常时更显著;当二者同时异常时,小颗粒的preβ1-HDL增加,大颗粒的HDL2b减少更加明显。直线相关和多元回归分析中发现,血浆TC、HDLC和LDLC含量紊乱与HDL亚类异常分布存在关联。结论 MS患者胆固醇含量与HDL亚类分布异常有关。     

微小RNA-17-5p通过靶向调控TP53INP1的表达对急性心肌梗死后心室重构的影响

目的：探讨微小RNA(miRNA)mi R-17-5p通过靶向调控肿瘤蛋白53诱导性核蛋白1(TP53INP1)的表达对急性心肌梗死(AMI)后心室重构的影响。方法：选取成年miR-17-5p^-/-、miR-17-5p^+/+和正常型SPF级昆明种小鼠各20只,采用随机数字表法分为假手术组、AMI组、miR-17-5p^-/-假手术组、miR-17-5p^-/-AMI组,miR-17-5p^+/+假手术组和miR-17-5p^+/+AMI组,每组10只,雌雄各半。构建小鼠AMI模型,采用超声心动图检测舒张末期容积指数(EDVI)、收缩末期容积指数(ESVI)和左室射血分数(LVEF),红四氮唑(TTC)染色法检测小鼠心肌梗死面积,实时定量聚合酶链反应(qRT-PCR)检测小鼠心脏组织miR-17-5p和TP53INP1 mRNA表达水平,Western blot法检测小鼠心脏组织TP53INP1蛋白表达水平。结果：与假手术组比较,AMI组建模后7 d和14 d的ED...     

Concerning the significance of paraoxonase-1 and SR-B1 genes in atherosclerosis

High-density lipoprotein (HDL) is an independent protective factor against cardiovascular disease. The enzyme paraoxonase-1 (PON-1) contributes to the anti-atherogenic effects of HDL. In vitro studies have demonstrated that paraoxonase's substrates are highly heterogeneous and that some contribute to the development of atherosclerotic lesions. The atheroprotective role of PON-1 was established in genetically engineered animal models. In humans, the PON-1 Gln192Arg and Met55Leu polymorphisms appear to be associated with increased susceptibility to cardiovascular disease and with different PON-1 activity levels and concentrations. The CLA-1 (CD36 and Lysosomal integral membrane protein-II Analogous-1) gene is the human homologue of the murine SR-B1 (Scavenger Receptor class B type 1) gene. SR-B1 was the first high-affinity HDL receptor to be identified at the molecular level. The CLA-1 receptor plays a pivotal role in HDL-mediated reverse cholesterol transport by mediating the selective uptake of free cholesterol as well as of native and oxidized cholesteryl esters. Its atheroprotective role has also been established in transgenic mice studies. Several polymorphic variants of the CLA-1 gene have been described, some of which are associated with phenotypic changes in plasma lipoproteins. Both genes participate in the complex HDL metabolic pathway and, presumably, also in defense mechanisms against oxidative stress.     

阿托伐他汀对高胆固醇血症患者清道夫受体BⅠ表达的影响

目的探讨清道夫受体BⅠ(SR-BⅠ)在动脉粥样硬化发生中的作用及阿托伐他汀抗动脉粥样硬化的作用机制。方法随机选择健康体检中心男性高TC血症患者60例为高脂组,另选男性TC正常者60例为对照组。采用紫外分光法检测血管紧张素转换酶(ACE)的活性,放射免疫法检测血管紧张素Ⅱ(AngⅡ)水平,硝酸还原酶法检测NO水平,RT-PCR和Western blot法分别检测SR-BⅠ mRNA和蛋白表达水平。结果与对照组比较,高脂组TC、TG、LDL-C、AngⅡ、ACE明显升高(P0.05,P0.01),HDL-C、NO、SR-BⅠ mRNA和蛋白表达明显降低(P0.05,P0.01);与同组治疗前比较,高脂组治疗后TC、TG、LDL-C、Ang Ⅱ、ACE明显降低(P0.05),HDL-C、NO、SR-BⅠ mRNA和蛋白表达明显升高(P0.05,P0.01)。HDL-C与SR-BⅠ呈显著正相关,AngⅡ与SR-BⅠ呈显著负相关。结论高TC血症患者SR-BⅠ表达降低,阿托伐他汀能上调SR-BⅠ表达。     

血浆miRNA在先天性心脏病继发肺动脉高压的差异表达

目的 探究先天性心脏病继发肺动脉高压（PAH）患者血浆中miRNA表达谱的差异,从而探究其与PAH的相关性。方法 先天性心脏病患者80例,根据肺动脉压力进行分组:肺动脉压正常者22例（无PAH组）;轻、中度PAH者37例（轻中度PAH组）;重度PAH者21例（重度PAH组）。另外选取门诊体检的志愿者20例作为对照组。采用定量聚合酶链反应（PCR）分析对比各组患者血浆miR-18a、miR-27b、miR-130a和miR-204的表达差异。分析miRNA表达水平与肺动脉压力的相关性。结果 与对照组相比,无PAH组、轻中度PAH组、重度PAH组患者miR-18a、miR-27b和miR-130a表达水平上调,miR-204的表达水平下调,差异有统计学意义（P<0.05）;与无PAH组相比,轻中度PAH组、重度PAH组患者miR-18a、miR-27b和miR-130a表达水平上调,miR-204的表达水平下调,差异有统计学意义（P<0.05）;与轻中度PAH组相比,重度PAH组患者miR-18a、miR-27b和miR-130a表达水平上调,miR-204的表达水平下调,差异有统计学意义（P<0.05）。Spearman线性相关分析显示血浆miR-18a、miR-27b和miR-130a表达水平与PAH呈正相关（r=0.845,r=0.912,r=0.933,P<0.05）;血浆miR-204的表达水平与PAH呈负相关（r=-0.629,P<0.05）。结论 miRNA在先天性心脏病继发PAH患者血浆中存在差异表达,miRNA的表达水平与肺动脉压力具有相关性。     

Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance

We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.     

H型高血压患者HDL亚组分的改变及对内皮细胞抗炎功能的影响

目的观察H型高血压患者血同型半胱氨酸水平(Hcy)与高密度脂蛋白(HDL)亚组分的相关性,并研究HDL亚组分对内皮细胞抗炎功能的影响。方法选取健康人群133例、单纯高血压患者76例、H型高血压患者85例,测定空腹血糖(FBG)、血清肌酐(SCr)、尿酸(UA)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)、HDL2、HDL3和Hcy等指标。分别留取各组血清各6例,应用快速蛋白液相色谱法(FPLC)提取大颗粒HDL(L-HDL),观察L-HDL对肿瘤坏死因子α(TNF-α)诱导的人脐静脉内皮细胞(HUVEC)炎症的改善作用。结果健康对照组、单纯高血压组和H型高血压组UA、FBG、TC、LDLC水平差异无统计学意义(P>0.05)。对比单纯高血压患者和健康对照组,H型高血压患者具有更低的HDLC、HDL2水平及更高的HDL3水平(P<0.001);血Hcy水平与血HDLC、HDL2呈显著负相关(P<0.01),但是与HDL3无显著相关性(P=0.083)。健康对照组、单纯高血压组L-HDL均可下调TNF-α诱导的血管内皮细胞表达血管细胞黏附分子1(VCAM-1),而H型高血压组L-HDL并不能明显减低VCAM-1表达。结论H型高血压患者可能通过高Hcy影响HDL的亚组分分布以及L-HDL对内皮细胞的抗炎功能。     

皮下免疫热休克蛋白65对小鼠巨噬细胞胆固醇流出率的影响及机制

目的观察皮下免疫不同剂量热休克蛋白65(HSP65)对载脂蛋白E缺失小鼠动脉粥样硬化及巨噬细胞TC流出率的影响。方法选择apoE-/-小鼠24只,随机分为磷酸盐缓冲液(PBS)对照组、5μg HSP65组及25μg HSP65组,每组8只,第3、6周进行皮下免疫。实验第16周末取标本,分离小鼠主动脉测定血管斑块面积;用自动生化仪测定小鼠血脂水平,酶联免疫吸附法分别检测血清HSP65抗体滴度及炎性因子白细胞介素10(IL-10)和干扰素γ水平,液闪计数仪检测巨噬细胞TC流出率;提取肝脏mRNA及膜蛋白,分别检测ATP结合盒转运蛋白A1(ABCA1)和G1(ABCG1)、B族Ⅰ型清道夫受体(SR-BⅠ)的表达。结果与PBS对照组比较,5μg HSP65组和25μg HSP65组TC流出率明显降低,HSP65抗体滴度和干扰素γ水平明显升高,主动脉粥样硬化斑块面积明显增加(P<0.05,P<0.01);其中25μg HSP65组血清HDL-C和IL-10表达较PBS对照组明显降低(P<0.01);5μg HSP65组和25μg HSP65组ABCA1、ABCG1及SR-BⅠmRNA表达明显低于PBS对照组(P<0.05)。结论皮下免疫HSP65可抑制小鼠巨噬细胞TC流出,可能是通过下调ABCA1、ABCG1和SR-BⅠ的表达。     

Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol

ObjectivePharmacological LXR activation has anti-atherosclerotic actions in animal models. Part of these beneficial effects may be explained by accelerated reverse cholesterol transport since both plasma high density lipoprotein (HDL) cholesterol and fecal neutral sterol secretion are higher upon LXR activation. Mechanisms underlying these LXR-mediated effects have not been fully elucidated.MethodsWe investigated the roles of the isoforms LXRα and LXRβ and the HDL cholesterol uptake receptor SR-B1 in modulation of cholesterol metabolism upon treatment of mice with the LXR ligand T0901317.ResultsHDL cholesterol was maximally 60% increased in a time-dependent fashion due to appearance of more and larger HDL particles. Fecal neutral sterol secretion was maximally induced after 1 week treatment. T0901317 treatment induced fecal neutral sterol secretion by ～300% in wild-type but not in Lxrα deficient mice. Surprisingly, LXR activation reduced SR-B1 protein amount in hepatic membranes, suggesting that this might contribute to elevated HDL cholesterol. However, T0901317 still elevated plasma HDL cholesterol in Sr-b1 deficient mice, suggesting that SR-B1 is not the only step involved in LXR-mediated induction of plasma HDL cholesterol. In addition, SR-B1 is not essential for LXR-induced cholesterol removal from the body.ConclusionInduction of fecal neutral sterol secretion by T0901317 critically depends on LXRα but not on LXRβ. LXR activation reduces SR-B1 in hepatic membranes, probably partly contributing to elevated HDL cholesterol. SR-B1 is not required to enhance fecal neutral sterol secretion.     

Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation

To test the hypothesis that apolipoprotein A-I (apoA-I) functions specifically to inhibit atherosclerosis independent of the level of high-density lipoprotein cholesterol (HDL-C) by promoting both reverse cholesterol transport and HDL antiinflammatory function in vivo, we established a murine atherosclerosis model of apoA-I deficiency in which the level of HDL-C is well maintained. ApoA-I-/- mice were crossed with atherosclerosis susceptible low-density lipoprotein receptor-/-/apobec-/- (LA) mice to generate LA mice with apoA-I+/+, apoA-I+/-, and apoA-I-/- genotypes. There were no major differences in the amounts of non-HDL-C and HDL-C in the plasma between different apoA-I genotypes. A significant inverse relationship was observed, however, between apoA-I gene dose and atherosclerosis in both female and male mice. Compared with LA-apoA-I+/+ mice, serum from LA-apoA-I-/- mice had a significantly reduced capacity to function as an acceptor of ABCA1- and SR-BI-mediated cellular cholesterol efflux, and also had markedly reduced lecithin cholesterol acyltransferase activity. In addition, LA-apoA-I-/- mice had significantly reduced macrophage-derived cholesterol esterification and reverse cholesterol transport in vivo. There was significantly reduced plasma paraoxonase (PON-1) activity, impaired HDL vascular antiinflammatory function, and increased basal levels of monocyte chemotactic protein-1 in the plasma of LA-apoA-I-/- mice compared with LA-apoA-I+/+ mice. In LA-apoA-I-/- mice, there was also greater induction of some, but not all, inflammatory cytokines and chemokines in response to intraperitoneal injection of lipopolysaccharide than in LA-apoA-I+/+ mice. We conclude that apoA-I inhibits atherosclerosis by promoting both macrophage reverse cholesterol transport and HDL antiinflammatory function, and that these anti-atherogenic functions of apoA-I are largely independent of the plasma level of HDL-C in this mouse model.     

胆固醇、甘油三酯、高密度脂蛋白与红细胞膜离子酶活性关系研究

目的探讨高血压时血浆胆固醇（Ｃｈｏ）、甘油三酯（ＴＧ）和高密度脂蛋白（ＨＤＬ－Ｃ）水平与细胞膜离子运输酶活性之间的关系。方法３２名正常人（ＮＴ）,５５例原发性高血压（ＨＴ）患者,检测血浆Ｃｈｏ、ＴＧ、ＨＤＬ－Ｃ水平,红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性,膜Ｃ／Ｐ克分子比率及膜内面Ｃａ２＋结合力。结果（１）ＨＴ组平均动脉血压（ＭＡＰ）与ＮＴ组相比有显著性差别;（２）ＨＴ组血浆ＨＤＬ－Ｃ水平、红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性,以及膜内面Ｃａ２＋结合力均较ＮＴ组明显减低;（３）ＨＴ组血浆Ｃｈｏ,ＴＧ水平、红细胞膜Ｃｈｏ含量和Ｃ／Ｐ克分子比率,与ＮＴ组比较皆明显增高。结论红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性减低,以及膜内面Ｃａ２＋结合力减低,是高血压时细胞膜离子运输失常的主要标志,血浆ＴＧ水平升高和膜磷脂水平减低可能是高血压时细胞膜理化特性及离子运输失常的主要决定因素。