代谢综合征患者血糖、血脂水平与HDL亚类组成的关系

目的:探讨代谢综合征(MS)患者血糖、血脂对血浆高密度脂蛋白(HDL)亚类组成及含量的影响。方法:收集MS患者组220例和对照组86例的血浆,采用全自动生化分析仪测定血脂及载脂蛋白的浓度,双向电泳-免疫印记检测法测定受试者HDL亚类的相对含量。结果:(1)与对照组相比,MS患者空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、LDL-C/高密度脂蛋白胆固醇(HDL-C)、载脂蛋白B100(apo B100)、apo B100/载脂蛋白A-I(apo A-I)、收缩压(SBP)、体重指数(BMI)与HDL3b含量均增加(P0.05),而HDLC、apo A-I、preβ2-HDL、HDL2a和HDL2b含量均减少(P0.01)。(2)随着血糖浓度的升高,血浆中HDL2a与HDL2b含量减少(P0.05),preβ1-HDL增加(P0.05)。(3)MS患者随着HDL-C含量的降低,HDL2b含量减少(P0.01),preβ1-HDL增加(P0.01)。(4)MS患者随着TG水平的增加和HDL-C水平的降低,血浆中小颗粒的preβ1-HDL有增加的趋势,而大颗粒的HDL2b有减少趋势,HDL成熟代谢受阻。(5)相关性分析发现FPG与大颗粒的HDL2a和HDL2b呈负相关;HDL-C与HDL2b呈正相关,而与preβ1-HDL呈负相关;TG含量与preβ1-HDL、HDL3b呈正相关。结论:MS患者随着血糖、TG含量的增加及HDL-C含量的减少,大颗粒的HDL2a和HDL2b含量减少,而小颗粒的preβ1-HDL含量增加,HDL颗粒有变小的趋势,HDL颗粒的成熟代谢受阻。     

血清总胆固醇、甘油三酯与高密度脂蛋白胆固醇比值同高密度脂蛋白亚类组成关系的研究

目的：探讨血清总胆固醇/高密度脂蛋白胆固醇(TC/HDL-C)、甘油三酯/高密度脂蛋白胆固醇（TG/HDL-C）比值与高密度脂蛋白（HDL）亚类组成及含量关系。 方法： 采用双向电泳-免疫印迹检测法分析了292例受试者血清HDL亚类的组成及含量。 结果： 随血清TC/HDL-C比值增大，preβ1-HDL、HDL3a含量升高，HDL2b、HDL2a含量降低。preβ1-HDL（P＜0.01，高比值组及中间组）、HDL3a（P＜0.05，高比值组）含量显著高于低比值组，而HDL2b（P＜0.01，高比值组及中间组）、HDL2a（P＜0.01，高比值组）含量显著低于低比值组；此外，高比值组preβ1-HDL、HDL3a含量显著高于中间组（P＜0.01，P＜0.05），而HDL2a、HDL2b含量显著低于中间组（P＜0.01，P＜0.01）。随血清TG/HDL-C比值增大，preβ1-HDL、HDL3a含量升高，HDL2b、HDL2a含量降低。preβ1-HDL、HDL3a（P＜0.01，P＜0.05，高比值组）含量显著高于低比值组，而HDL2b、HDL2a（P＜0.01，P＜0.01，高比值组及中间组）含量显著低于低比值组；此外，高比值组preβ1-HDL、HDL3a含量显著高于中间组（P＜0.01，P＜0.05），而HDL2a、HDL2b含量显著低于中间组（P＜0.01，P＜0.01）。相关分析发现，血清TC、TG、TC/HDL-C、TG/HDL-C与小颗粒preβ1-HDL含量呈显著正相关（P＜0.01，P＜0.01，P＜0.01，P＜0.01），与大颗粒HDL2b含量呈显著负相关（P＜0.05，P＜0.01，P＜0.01，P＜0.01）；HDL-C与小颗粒preβ1-HDL含量呈显著负相关（P＜0.05），与大颗粒HDL2b含量呈显著正相关（P＜0.01）。 结论： 血清TC/HDL-C＞5或TG/HDL-C＞2.2时，小颗粒HDL含量明显增加而大颗粒HDL含量明显减少，表明HDL成熟代谢过程受阻，胆固醇逆向转运作用减弱。     

血清载脂蛋白CⅡ含量对HDL亚类分布的影响

目的:探讨血清载脂蛋白CⅡ含量对HDL亚类分布的影响。方法:采用双向电泳-免疫印迹方法检测247例受试者血清HDL亚类组成及含量。结果:随血清apoCⅡ水平的逐渐升高,年龄、BMI、TG、TC、apoB100、apoCⅡ、apoCⅢ、apoE、preβ1-HDL、preβ2-HDL、HDL3b和HDL3a含量显著增加,HDL-C、HDL2a、HDL2b含量显著减少。随apoCⅡ和apoAⅠ水平的逐渐升高,preβ1-HDL的含量均呈增加趋势,但HDL2b的含量在同一apoCⅡ组随apoAⅠ水平的升高呈增加趋势,而在同一apoAⅠ组随apoCⅡ水平的增加呈减少趋势。随apoCⅡ/apoCⅢ比值的逐渐升高,preβ1-HDL的含量呈增加趋势,而HDL2b的含量呈减少趋势。相关分析发现,控制血清TG和TC浓度后,apoCⅡ与preβ1-HDL呈显著正相关(r=0.186,P0.01),与HDL2b呈显著负相关(r=-0.149,P0.05);apoAⅠ含量与所有HDL亚类呈显著正相关(r值在0.349-0.587之间,P0.01);此外,apoCⅢ与preβ1-HDL和preβ2-HDL呈显著正相关(r分别为0.184和0.178,P0.01);apoB100与HDL2a呈显著负相关(r=-0.102,P0.05);apoE与HDL3a呈显著正相关(r=0.040,P0.05)。结论:随血清apoCⅡ水平的逐渐升高,HDL亚类的颗粒呈减小趋势,提示HDL成熟代谢受阻;apoAⅠ的含量可以对抗apoCⅡ对HDL亚类分布的影响;apoCⅡ/apoCⅢ的比值亦可作为反映HDL亚类分布的指标之一。     

血清HDL亚类分布特征及与载脂蛋白的关系

目的：分析人群中HDL各亚类的频数分布特征及探讨载脂蛋白含量与HDL亚类含量、分布变化的关系。方法:采用双向电泳-免疫印迹方法检测血清HDL亚类含量，Kolmogorov-Smirnov检验HDL亚类分布类型,直线相关及多元线性回归分析血清HDL亚类分布与载脂蛋白关系。结果:血清preβ2-HDL、HDL3a、HDL2a、HDL2b呈正态分布，preβ1-HDL、HDL3b、HDL3c呈偏态分布；女性HDL-C、apoAI、HDL2a及HDL2b的含量显著高于男性，而preβ1-HDL及HDL3c的含量则显著低于男性；相关分析发现apoAI含量与所有亚类的水平呈显著正相关（r值在0.365-0.577范围，P<0.01），apoB100、apoCII、apoCIII、apoE与Preβ1-HDL及HDL3a的水平呈显著正相关（r值在0.139-0.489范围，P<0.01），但与HDL2a、HDL2b的水平呈显著负相关（r值在-0.122~-0.386范围，P<0.01）；多元线性回归分析表明：apoAI对HDL各亚类含量变化影响最大（β值在0.385-0.601范围,P<0.01）。结论:血清preβ2-HDL、HDL3a、HDL2a、HDL2b呈正态分布，preβ1-HDL、HDL3b、HDL3c呈偏态分布。apoAI与HDL各亚类含量均呈显著正相关并且对亚类含量变化的影响最大;apoB100及apoCII、apoCIII和apoE与小颗粒的Preβ1-HDL呈显著正相关（r值在0.355-0.489范围，P<0.01），而与大颗粒的HDL2a或HDL2b呈显著负相关（r值在-0.122~-0.386范围，P<0.01）。     

成都地区中老年人高脂血症患者血清HDL亚类组成的研究

目的：探讨中老年人高脂血症患者血清HDL亚类组成和相对百分含量的变化及其与血脂水平的关系。方法： 采用双向电泳-免疫印迹检测法按年龄分层分析了172例中老年人高脂血症患者及115例正常中老年对照血清HDL亚类组成及相对百分含量。结果: 中老年人高脂血症患者血清中小颗粒的preβ1-HDL、HDL3b、HDL3a含量显著高于对照组（P＜0.01或P＜0.05），而大颗粒的HDL2b含量显著低于对照组（P＜0.01）；正常健康中老年人发现随着年龄的增长，preβ1-HDL有逐渐升高的趋势，HDL2b有降低的趋势，中老年高脂血症患者及正常对照，各年龄组中均可见男性preβ1-HDL含量显著高于女性（P＜0.05），HDL2b含量显著低于女性（P＜0.05）。此外，相关分析发现中老年人高脂血症组小颗粒的preβ1-HDL含量与患者血清TG、TC、apoB100、apoCⅡ、apoCⅢ、apoE水平及TG/HDL-C比值呈显著正相关（r=0.432；r=0.243；r=0.341；r=0.259；r=0.335；r=0.308及r=0.453，P＜0.05或P＜0.01），与HDL-C水平呈显著负相关（r=－0.167，P＜0.05）；与此相反，大颗粒的HDL2b水平与TG、TC、apoCⅡ、apoCⅢ、apoE水平及TG/HDC比值呈显著负相关（r=－0.296；r=－0.156；r=－0.182；r=－0.216；r=－0.203及r=－0.313，P＜0.05或P＜0.01），而与HDL-C水平呈显著正相关（r=0.124，P＜0.05）。结论: 中老年人高脂血症患者血清HDL亚类颗粒呈变小趋势，且男性HDL颗粒较女性小，中老年高脂血症患者胆固醇逆向转运过程可能减弱。     

血清甘油三酯含量与HDL亚类组成的关系

目的：探讨血TG含量对HDL亚类组成及含量的影响。 方法： 采用双向电泳－免疫印迹检测法按血清TG含量分层，分析了106例TC正常及147例高TC受试者血清HDL亚类组成及含量。 结果： 无论TC正常或高TC人群，血清小颗粒的per-β1-HDL含量在TG边缘性高（TC正常人群除外）、高TG以及TG极高亚组显著高于相应TG正常组 (P＜0.05及P＜0.01），而且颗粒较小的HDL3b及HDL3a含量也有相似的变化，其中高TG人群HDL3b在TG极高组，HDL3a在TG升高的各亚组均显著高于TG正常亚组(P＜0.05及P＜0.01）；与此相反，大颗粒的HDL2b在高TG组和TG极高组显著少于相应的TG正常亚组（p＜0.05），HDL2a也在高TC人群的TG极高组显著少于TG正常亚组（P＜0.05）。此外，与TC正常的相应亚组比较，高TC人群的per-β1-HDL（TG边缘性高亚组）及HDL3b（TG极高亚组）显著高于TC正常人群的相应亚组（P＜0.05及P＜0.01）。 结论： 随着TG、TC水平的升高，血清HDL颗粒呈变小趋势；TG、TC含量变化是影响HDL亚类组成的重要因素。     

血清超敏C反应蛋白水平及TC/HDL比值与冠脉次全闭塞病变的关系

目的:探讨血清超敏C反应蛋白(hs-CRP)水平及总胆固醇/高密度脂蛋白比值(TC/HDL)与冠心病次全闭塞病变的关系。方法:冠心病冠脉次全闭塞病变组89例,非次全闭塞病变117例为对照组,测定两组血清hs-CRP水平,计算TC/HDL比值,比较两组间差异。以Logistic回归分析血清hs-CRP水平、TC/HDL比值是否能独立预测冠心病次全闭塞病变,并计算其相对危险度(以OR值表示)。结果:次全闭塞病变组hs-CRP水平(5.22±2.88mg/L)明显低于对照组(9.15±6.56mg/L),P<0.01,TC/HDL比值(4.51±1.37)明显高于对照组(3.75±0.75),P<0.01。Logistic回归分析表明hs-CRP≤5mg/L(OR=3.26,P<0.01)、TC/HDL比值≥4(OR=2.88,P<0.01)可独立预测次全闭塞病变。结论:低血清hs-CRP水平及高TC/HDL比值是冠心病冠脉次全闭塞病变的独立预测因素。     

血浆载脂蛋白A5水平与HDL亚类分布的关系

目的：探讨载脂蛋白A5（apolipoprotein A5,apoA5）水平对HDL亚类分布的影响。方法：采用酶联免疫吸附法（enzyme-1inked immunosorbent assay,ELISA）和双向电泳免疫印迹检测法分别检测310例受试者的血浆apoA5浓度和HDL亚类相对含量。受试者按apoA5浓度均值加或减去一个标准差作为分割点,分为高apoA5组（apoA5≥286．83mg／L）,中apoA5组（139．99mg／L≤apoA5〈286．83mg／L）和低apoA5组（apoA5〈139．99mg／L）。结果：与高apoA5组相比,apoA5低浓度组preβl-HDL和HDL3a含量显著升高（P〈0．01）,HDL2a和HDL2b显著降低（p〈0．01）。结论：随着血浆apoA5浓度降低,HDL亚类有变小的趋势,apoA5浓度降低可能阻碍了HDL亚类的成熟。     

鸭血清卵磷酯-胆固醇-酰基转移酶的提取、纯化与鉴定

卵磷酯—胆固醇—酰基转移酶(LCAT)是酯化高密度脂蛋白(HDL)胆固醇的关键酶,在血浆脂蛋白代谢中起着重要作用。最近几个实验室已将此酶从人和一些哺乳动物的血浆中纯化成单体。鸭血清脂蛋白的HDL含量很高,是研究HDL中胆固醇酯化的较好的模型。为了研究血清脂蛋白的代谢机制,我们从鸭血清中提取纯化了LCAT。方法、结果如下:取新鲜鸭血清,先对Ⅰ=0.1的磷酸盐缓冲液透析,再用硫酸葡聚糖和CaCl_2(终浓度分别为1.4％和0.1M)沉     

高密度脂蛋白亚类与蛋白激酶C活性的关系

目的：观察高密度脂蛋白（HDL）亚类与外周细胞和肝细胞HDL受体结合活性及细胞PKC活性的关系。方法： 以纯化的前β1-HDL及不含apoE的HDL3为配体，分别与人动脉平滑肌细胞（SMC）和肝癌细胞系HepG2反应，观察两种细胞HDL受体结合活性及细胞PKC活性的变化。结果： 前β1-HDL与SMC HDL受体的亲和力不仅显著高于不含apoE的HDL3与SMC HDL受体的亲和力（P＜0.05），而且还显著高于它与HepG2细胞HDL受体的亲和力（P＜0.05）；前β1-HDL和不含apoE的HDL3分别与SMC反应后，均可激活细胞PKC信号传递途径，且前β1-HDL的作用较不含apoE的HDL3更为明显；而这二种HDL亚类分别与HepG2细胞反应后，细胞PKC活性均无明显变化。结论： 前β1-HDL似乎可以比不含apoE的HDL3更为有效的促进细胞胆固醇移出，而且血浆中前β1-HDL可能更多地作用于外周细胞如SMC，并通过外周细胞膜上的HDL受体介导激活PKC信号传递途径，从而促进外周细胞中过剩的胆固醇移出，而肝细胞HDL受体介导的胆固醇进入细胞可能与PKC信号途径无关。     

Detection of qualitative abnormalities of HDL by measurement of prebeta1-HDL concentration

Prebeta1-HDL is a native lipid-poor HDL that promotes cholesterol efflux from cell membranes. Prebeta1-HDL is a good substrate of lecithin-cholesterol acyltransferase (LCAT) and is converted into a-migrating spherical HDL by LCAT activity. Prebeta1-HDL is probably secreted from the liver and is also generated from a-HDL by several regulatory factors. At present, prebeta1-HDL concentration is determined by native two-dimensional gel electrophoresis, ultrafiltration-isotope dilution method, or immunoassay using monoclonal antibody. Plasma samples for immunoassay are pretreated with 50% sucrose, which stabilizes prebeta1-HDL during storage at -20 degrees C as well as at 4 degrees C. We determined the LCAT-dependent conversion rate of prebeta1-HDL to detect abnormal HDL metabolism. In this review, we discuss the physiological role of prebeta1 HDL and the clinical significance of plasma prebeta1-HDL concentration.     

Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein,serum lipoprotein and glucose levels

The present authors investigated the individual and combined associations of the apolipoprotein (apo) A-I -75 bp and +83 bp polymorphisms with plasma lipid, lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The frequency of the A allele at position -75 bp (G-->A) was 0.14 in women and 0.17 in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C-->T and G-->A, respectively) were 0.04 and 0.05 in women and men, respectively. In women, the A allele was associated with significantly higher levels of apo B (P = 0.016), total cholesterol (TC) (P = 0.005), low-density lipoprotein cholesterol (LDL-C) (P = 0.018) and TC:high-density lipoprotein (HDL) ratio (P = 0.026) compared to the G/G subjects. In men, no significant associations were detected between the -75 bp polymorphism and any lipid trait examined. The M2 allele for the +83 bp polymorphism was significantly associated in men with higher levels of apo A-I (P = 0.002) and TC (P = 0.046). In women, a significant effect was observed for TC (P = 0.036), with M2+/- subjects having lower levels than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the apo A-I -75 bp and +83 bp polymorphisms was detected. Women carrying both rare alleles (G/A M2+/-) had significantly higher TC:HDL ratios (P = 0.031) compared to the other haplotypes. In men, significant differences were observed for apo A-I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/- haplotype having the highest values compared to other genotype combinations. In conclusion, the -75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B, plasma TC and LDL-C in women, while the +83 bp polymorphism seems to affect the apo A-I levels in men, and the plasma cholesterol levels in both genders.     

Clinical presentation, laboratory values, and coronary heart disease risk in marked high-density lipoprotein-deficiency states

Our purpose is to provide a framework for diagnosing the inherited causes of marked high-density lipoprotein (HDL) deficiency (HDL cholesterol levels <10 mg/dL in the absence of severe hypertriglyceridemia or liver disease) and to provide information about coronary heart disease (CHD) risk for such cases. Published articles in the literature on severe HDL deficiencies were used as sources. If apolipoprotein (Apo) A-I is not present in plasma, then three forms of ApoA-I deficiency, all with premature CHD,and normal low-density lipoprotein (LDL) cholesterol levels have been described: ApoA-I/C-III/A-IV deficiency with fat malabsorption, ApoA-I/C-III deficiency with planar xanthomas, and ApoA-I deficiency with planar and tubero-eruptive xanthomas (pictured in this review for the first time). If ApoA-I is present in plasma at a concentration <10 mg/dL, with LDL cholesterol that is about 50% of normal and mild hypertriglyceridemia, a possible diagnosis is Tangier disease due to mutations at the adenosine triphosphate binding cassette protein A1 (ABCA1) gene locus. These patients may develop premature CHD and peripheral neuropathy, and have evidence of cholesteryl ester-laden macrophages in their liver, spleen, tonsils, and Schwann cells, as well as other tissues. The third form of severe HDL deficiency is characterized by plasma ApoA-I levels <40 mg/dL, moderate hypertriglyceridemia, and decreased LDL cholesterol, and the finding that most of the cholesterol in plasma is in the free rather than the esterified form, due to a deficiency in lecithin:cholesterol acyltransferase activity. These patients have marked corneal opacification and splenomegaly, and are at increased risk of developing renal failure, but have no clear evidence of premature CHD. Marked HDL deficiency has different etiologies and is generally associated with early CHD risk.     

Cigarette smoke-induced depression in LCAT activity

The effect of acute inhalation of cigarette smoke on plasma cholesterol esterification by lecithin-cholesterol acyltransferase (LCAT) in atherosclerosis-susceptible White Carneau pigeons was examined. Pigeons were assigned to four treatment groups: (1) Shelf Control fed a chow diet and not exposed to smoke products; (2) Sham pigeons fed a cholesterol-saturated fat diet and exposed to fresh air by the Lorillard smoking machine; (3) low nicotine-low carbon monoxide (LoLo) animals also fed the cholesterol diet and exposed to low concentrations of these cigarette smoke products; and (4) high nicotine-high carbon monoxide (HiHi) birds fed the cholesterol diet and subjected to high concentrations of these inhalants. Both Control and Sham birds had significantly higher LCAT activity (percentage esterification per minute) than HiHi pigeons. Experiments designed to determine whether altered enzyme and/or substrate were responsible for depressed activity revealed no smoke-related modification in substrate efficiency. In addition, Sham and HiHi pigeons had similar concentrations of plasma-free cholesterol, high density lipoprotein (HDL) cholesterol, cholesteryl ester and phospholipid, and similar HDL phospholipid and cholesteryl ester fatty acid profiles. However, reduced LCAT activity in HiHi pigeons can be explained by (1) impairment of enzyme efficiency as estimated by in vitro analysis; and (2) in vivo reduction in levels of LCAT cofactor, HDL apoprotein A-I.     

A first British case of fish-eye disease presenting at age 75 years: a double heterozygote for defined and new mutations affecting LCAT structure and expression.

Fish-eye disease is a familial syndrome with corneal opacification, major high density lipoprotein (HDL) deficiency in plasma, significant cholesterol esterification in plasma on non-HDL lipoproteins, generally without premature coronary disease. This first British male case from unrelated British parents had infarcts when aged 49 and 73 years but was asymptomatic at age 81 years, with plasma cholesterol 4.3-7.1 mmol/litre, triglycerides 1.8-2.2 mmol/litre, HDL cholesterol < 0.1 mmol/litre, apolipoprotein A-I < 0.16 g/litre, lipoprotein(a) 0.61 g/litre. Cholesterol esterification was impaired using HDL-3 and A-I proteoliposomes but not using VLDL/IDL/LDL. The findings are those of LCAT deficiency with the classic fish-eye disease defect. Most of the 22 reported cases were homozygous or heterozygous for a Thr-Ile mutation at codon 123 of the lecithin:cholesterol acyltransferase (LCAT) gene. This patient was a double heterozygote for this mutation and a second new incompletely defined mutation affecting LCAT expression as defined by reduced mass and activity in plasma.