脑卒中患者血浆HDL亚类组成及与血压的相关性

目的研究脑卒中患者高密度脂蛋白(high density lipoprotein,HDL)亚类组成及相对百分含量的变化,并探讨脑卒中患者血压与HDL亚类组成的关系。方法采用双向电泳-免疫印迹检测法分析了79例正常对照和98例脑卒中患者HDL亚类组成及相对百分含量。结果脑梗死组preβ1-HDL(P<0.05或P<0.001)、HDL3c(P<0.001)水平显著增加,而HDL2a(P<0.05)及HDL2b(P<0.05或P<0.001)水平显著减少。脑出血组preβ1-HDL、HDL3c含量显著增加(P<0.05),而HDL2b含量显著减少(P<0.001)。受试者按收缩压水平分组发现,随着收缩压水平逐渐升高,小颗粒的preβ1-HDL、HDL3c及HDL3a水平均有升高趋势,而大颗粒的HDL2b水平有降低趋势。与正常组比较,收缩压高组(组Ⅳ:160 mmHg≤收缩压<180 mmHg)及收缩压极高组(组V:收缩压≥180 mmHg)preβ1-HDL、HDL3c含量均显著升高(P<0.05),而HDL2b含量显著降低(P<0.05)。且收缩压水平与preβ1-HDL、HDL3c水平呈正相关(r=0.235,r=0.250),而与HDL2b水平呈负相关(r=-0.228)。结论脑卒中患者HDL颗粒直径呈变小趋势,并且随着收缩压水平升高,其HDL颗粒的变小程度更加明显。     

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。     

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。     

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。     

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。     

2型糖尿病患者血清HDL亚类组成的研究

目的研究2型糖尿病患者血清HDL亚类组成及相对百分含量的变化.方法采用双向电泳-免疫印迹检测法分析了38例正常对照及38例患者血清HDL亚类组成及相对百分含量.结果患者血清中前β1-HDL(P＜0.001)、前β2-HDL及HDL3a(P＜0.05)含量显著增加,而HDL2a(P＜0.05)及HDL2b(P＜0.001)含量显著减少.患者空腹血糖及血清TG浓度与前β1-HDL、HDL3c及HDL3a水平呈显著正相关,而与HDL2b水平呈显著负相关.结论2型糖尿病患者血清HDL颗粒直径呈变小趋势,提示患者HDL成熟代谢过程受阻.     

血浆晚期氧化蛋白产物与HDL亚类组成的关系

目的 探讨血浆晚期氧化蛋白产物(AOPPs)对血浆高密度脂蛋白(HDL)亚类组成及含量的影响.方法 采用氯胺-T法和双向电泳免疫印迹检测法对346例受试者分别测定血浆AOPPs的相对含量和血浆HDL亚类的组成及含量.按AOPPs浓度均值加或减去一个标准差作为分割点,将受试者分为3组,即低AOPPs(AOPPs≤60μmol/L)组、中AOPPs(60 μmol/L＜ AOPPs ＜90 μmol/L)组、高AOPPs(AOPPs ≥90μmol/L)组.结果 与低AOPPs组相比,高AOPPs组中preβ1-HDL及HDL3a显著增多(P＜0.001),而HDL2a、卵磷脂胆固醇酰基转移酶及HDL2b显著降低(P＜0.001),各组胆固醇酯转运蛋白无变化.相关性分析表明AOPPs与血浆HDL亚类分布存在显著相关.结论 随着血浆AOPPs水平的升高HDL颗粒有变小的趋势,AOPPs可能阻碍了HDL的成熟代谢.     

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。     

不同类型高脂血症患者血清高密度脂蛋白亚类组成的研究

目的 :探讨不同类型高脂血症患者血清高密度脂蛋白 (HDL)亚类组成和相对百分含量的变化及其之间的差异。方法 :采用双向电泳 免疫印迹检测法分析了 39例高胆固醇 (TC)血症患者、97例高甘油三酯 (TG)血症患者及 32例混合性高脂血症 (MHL)患者血清HDL亚类组成及相对百分含量。结果 :高TC、高TG及MHL患者血清中小颗粒的前 β1 HDL、前 β2 HDL、及HDL3b 含量显著增加 (P<0 .0 5 ～ <0 .0 1) ,而大颗粒的HDL2a及HDL2b含量显著减少 (P <0 .0 5～<0 .0 1)。高TC患者血清中HDL2b含量显著高于高TG及MHL患者 (P <0 .0 1及P<0 .0 5 ) ,而前 β1 HDL含量低于或显著低于高TG及MHL患者 (P<0 .0 1) ;高TG患者血清中HDL3a含量显著高于高TC及MHL患者 (P<0 .0 1) ,而HDL2b含量均较其他二者为低。结论 :高TC、高TG及MHL患者血清HDL颗粒直径均呈变小趋势 ,但其HDL亚类组成的具体变化特征却有一定差异。     

Ⅳ型高脂血症患者高密度脂蛋白亚类组成与脂蛋白酯酶基因多态性的关系

目的:探讨Ⅳ型高脂血症(ⅣHL)患者高密度脂蛋白(HDL)亚类组成与脂蛋白酯酶基因多态性的关系。方法:采用聚合酶链反应限制性片段长度多态性和双向电泳免疫印迹检测法,分析104例ⅣHL患者和107例血脂正常者的脂蛋白酯酶基因内含子8HindⅢ酶切位点多态性、HDL亚类组成及相对百分含量。结果:ⅣHL组和对照组均以H H 纯合子基因型为主,ⅣHL患者H 等位基因频率较对照组增加,而H-H-等位基因频率显著降低(P<0.05)。ⅣHL组和对照组H H 基因型者与H-H-者比较,血浆TG、TG/HDLC比值明显升高,Ⅳ型HL组H H 基因型者与H-H-者比较,HDL小颗粒的preβ1HDL、HDL3a相对含量增多,大颗粒的HDL2a、HDL2b相对含量减少,其差异有统计学意义(P<0.05)。结论:ⅣHL患者脂蛋白酯酶基因多态性与HDL亚类的组成及成熟代谢相关。     

Relationship between total cholesterol/high-density lipoprotein cholesterol ratio, triglyceride/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442 Chinese subjects. The particle size of HDL shifted toward smaller size with the elevation of TC/HDL-C and TG/HDL-C ratios. The ratio of large-sized HDL(2b) to small-sized prebeta(1)-HDL (HDL(2b)/prebeta(1)-HDL) was about 4.7 in the subjects with TC/HDL-C of 3.3 or lower and TG/HDL-C of 2.5 or lower, whereas it was only approximately 1.1 in subjects with TC/HDL-C greater than 6 and TG/HDL-C greater than 5. Pearson correlation analysis revealed that the TC/HDL-C ratio was positively correlated with prebeta(1)-HDL and HDL(3a) but negatively correlated with HDL(2a) and HDL(2b), whereas the TC/HDL-C ratio was only inversely correlated with HDL(2b). The TC/HDL-C and TG/HDL-C ratios together may be a good indicator of HDL subclass distribution. When these 2 ratios increased simultaneously, the trend toward smaller HDL size was obvious, which, in turn, indicated that the maturation of HDL might be impeded and the reverse cholesterol transport might be weakened. In addition, the TG/HDL-C ratio might be a more powerful factor to influence the distribution of HDL subclasses.     

The relationship between high density lipoprotein subclass profile and apolipoprotein concentrations

The HDL fraction in human plasma is heterogeneous in terms of size, shape, composition, and surface charge. The HDL subclasses contents were quantified by 2-dimensional non-denaturing gel electrophoresis, immunoblotting, and image analysis. This research review systematically analyzed the relationship between the contents of HDL subclasses and the concentrations and ratios of the 5 major plasma apolipoproteins (apo). As the concentration of apoA-I increases, the contents of all HDL subclasses increase significantly. The most significant association was observed between large-sized HDL2b contents and apoA-I. ApoA-II played a dual function in the contents of HDL subclasses, and both small-sized HDL3b and HDL3a and large-sized HDL2b tended to increase with apoA-II concentration. An increase in the concentrations of apoC-II, C-III, and B-100 resulted in higher levels of small-sized HDL particles and lower levels of large-sized HDL particles. Plasma apoB- 100, apoC-II, and apoC-III appear to play a coordinated role in assembly of HDL particles and the determination of their contents. Higher concentrations of apoA-I could inhibit the reduction in content of large-sized HDL2b effected by apoB-100, C-II, and C-III. The preβ1-HDL contents increased significantly and those of HDL2b declined progressively with an increased apoB-100/apoA-I or a decreased apoC-III/apoC-II ratio. In summary, each apo has distinct but interrelated roles in HDL particle generation and metabolism. ApoA-I and apoC-II concentrations are independent determinants of HDL subtypes in circulation and apoA-I levels might be a more powerful factor to influence HDL subclasses distribution. Moreover, apoB- 100/apoA-I ratio could reliably and sensitively reflect the HDL subclass profile.     

Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling

Probucol is a unique hypolipidemic agent that increases cholesteryl ester transfer protein (CETP) activity. Enhanced CETP-mediated conversion of high-density lipoprotein (HDL) partly explains the probucol-induced decrease in HDL cholesterol and increase in plasma preβ1-HDL (native lipid-poor HDL) concentrations. However, HDL cholesterol is reduced in patients that are completely deficient in CETP. Angiopoietin-like protein 3 (ANGPTL3) is an endogenous suppressor of endothelial lipase that promotes the hydrolysis of HDL phospholipids and may generate preβ1-HDL. To determine whether probucol decreases ANGPTL3 and HDL phospholipids while increasing preβ1-HDL, we measured these parameters before and after a 4-week probucol treatment in 39 hypercholesterolemic patients and age- and sex-matched controls. The median ANGPTL3 had decreased from 143 to 113 μg/L by week 4 (p < 0.05). High-performance liquid chromatography revealed that probucol decreased the phospholipid content of very large (13.5–15 nm) and large (12.1 nm) HDL particles predominantly by 65% (p < 0.01) and 53% (p < 0.001), respectively. The change in ANGPTL3, but not CETP mass, was positively correlated with that in large HDL phospholipids (r = 0.455, p < 0.05). The absolute and relative concentrations of preβ1-HDL increased by 14% (p < 0.01) and 60% (p < 0.001), respectively. The conversion rate of preβ1-HDL into α-migrating HDL by lecithin-cholesterol acyltransferase did not change significantly. In conclusion, probucol decreases plasma ANGPTL3 and HDL phospholipids while increasing preβ1-HDL. We speculate that probucol induces HDL remodeling via an endothelial lipase-mediated pathway.     

The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome

Objective:  We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS).
Methods:  Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay.
Results:  We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy.
Conclusion:  OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.     

Pitavastatin decreases plasma prebeta1-HDL concentration and might promote its disappearance rate in hypercholesterolemic patients

AIM: Prebeta1-HDL is involved in the initial step of cholesterol efflux from peripheral cells and plays an important role in reverse cholesterol transport. We studied the effect of pitavastatin on the HDL subfraction profile, prebeta1-HDL concentration and its disappearance rate. METHODS: Twenty-nine hypercholesterolemic patients were treated with pitavastatin at 2 mg/day for 4 weeks, and plasma levels of total cholesterol (TC), triglyceride, HDL-cholesterol (C), HDL(2)-C, HDL(3)-C, prebeta1-HDL, LCAT activity, and CETP mass were assayed. The prebeta1-HDL disappearance rate was determined as the difference in prebeta1-HDL concentration before and after incubation at 37 degrees C for 90 min divided by the pre-incubation prebeta1-HDL concentration. RESULTS: Pitavastatin led to significant decreases in TC by 26.9% and LDL-C by 39.8%. HDL-C and HDL(2)-C increased significantly by 6.0% and 9.0%, respectively, but there was no significant change in HDL(3)-C. Prebeta1-HDL concentration significantly decreased (-8.7%; p<0.05); however, its disappearance rate significantly increased (13.0%; p<0.05). There were significant decreases in both LCAT activity and CETP mass. CONCLUSION: Although pitavastatin decreased plasma prebeta1-HDL concentration, it increased the prebeta1-HDL disappearance rate. These data suggest that pitavastatin might promote the early step of reverse cholesterol transport.     

Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of apo B-100, C-II, and C-III were higher, whereas those of HDL cholesterol were lower, for subjects in the highest tertile of apo C-III levels group, which presented a typical hypertriglyceridemic lipid profile. Subjects in the middle and highest tertile of apo C-III levels groups had increased preβ₁-HDL, HDL_3c, HDL_3b (only in the highest tertile of apo C-III group), and HDL_3a, but decreased HDL_2a and HDL_2b contents compared with subjects in the lowest tertile of apo C-III levels group. With the elevation of apo C-III together with apo C-II levels, contents of small-sized preβ₁-HDL increased successively and significantly; but those of large-sized HDL_2b reduced successively and significantly. With a rise in apo C-III and apo A-I levels, those of preβ₁-HDL increased significantly. Moreover, subjects with high apo A-I levels showed a substantial increase in HDL_2b; on the contrary, HDL_2b declined progressively and obviously for subjects in the low apo A-I levels with the elevation of apo C-III levels. Correlation analysis illustrated that apo C-III levels were positively associated with preβ₁-HDL, preβ₂-HDL, and HDL_3a. The particle size of HDL shifted toward smaller sizes with the increase of plasma apo C-III levels, and the shift was more remarkable when the elevation of apo C-III and apo C-II was simultaneous; and besides, higher apo A-I concentrations could modify the effect of apo C-III on HDL subclass distribution profile. Large-sized HDL_2b particles decreased greatly for hypertriglyceridemic subjects who were characterized by elevated apo C-III and C-II accompanied with significantly lower apo A-I, which, in turn, blocked the maturation of HDL.     

不同糖耐量人群血浆载蛋白A5与胰岛B细胞第一时相胰岛素分泌关系研究

目的探讨不同糖耐量人群血浆载脂蛋白A5(apolipoprotein A5,apoA5)与胰岛B细胞第一时相胰岛素分泌的关系。方法选取2009年2月至9月重庆医科大学附院门诊35例新诊断的2型糖尿病(T2DM组),30例糖调节受损者(IGR组),35例正常对照(NGT组)。以葡萄糖刺激后3～5 min急性胰岛素反应(AIR3-5)来表示第一时相胰岛素分泌功能指数;测空腹apoA5、游离脂肪酸(FFA)及糖负荷后2hFFA(2hFFA);稳态模型评价胰岛素抵抗指数(HOMA-IR)及胰岛B细胞功能(HOMA-β)。探讨apoA5与AIR3-5、血脂、血糖、HOMA-B及HOMA-IR等关系。结果(1)T2DM组、IGR组的apoA5、AIR3-5、HDL-C、HOMA-B显著低于NGT组(P<0.05),且T2DM组显著低于IGR组(P<0.05);(2)T2DM组、IGR组TG、FFA、2hFFA、LDL-C、FPG、2hPG、FINS、BMI、WHR和HOMA-IR明显高于NGT组(P<0.05),T2DM组显著高于IGR组(P<0.05);(3)apoA5与AIR3-5、HOMA-B、HDL-C均呈正相关,与TG、FFA、2hFFA、LDL-C、FPG、2hPG、FINS、HOMA-IR、BMI、WHR均呈负相关;(4)多元逐步回归分析显示,AIR3-5、TG、FFA、WHR、HOMA-IR是apoA5的独立影响因素。结论从NGT到IGR到T2DM发病进程中,低apoA5血症可能通过升高FFA而导致高甘油三酯血症,使B细胞第一时相胰岛素分泌受损,故推测升高apoA5水平,可能会降低TG,从而改善和恢复第一时相胰岛素分泌,延缓T2DM的进程。     

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.     

Bezafibrate increases prebeta 1-HDL at the expense of HDL2b in hypertriglyceridemia

Prebeta1-high density lipoprotein (prebeta1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL(2) by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase prebeta1-HDL at the expense of HDL(2). To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglycerides>2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, prebeta1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5+/-49.9 versus 72.5+/-34.1 mg/L apoA-I, P<0.01). Prebeta1-HDL was positively correlated with triglyceride (r=0.624, P<0.0001). A 4-week bezafibrate treatment (400 mg daily) increased prebeta1-HDL by 30% (160.2+/-64.5 mg/L apoA-I, P<0.05) but decreased HDL(2b) by 31% (from 188.8+/-94.9 to 129.3+/-78.7 mg/L apoA-I, P<0.05). Hepatic lipase activity increased by 24% (P<0.005). Prebeta1-HDL was generated either from ultracentrifugally isolated HDL(2) or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases prebeta1-HDL at the expense of HDL(2). We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.