糖尿病患者Apo－Al、Apo－B测定及其临床意义

本文对６０例糖尿病患者及６２例正常人的血清载脂蛋白（Ａｐｏ）－Ａｌ，Ａｐｏ－Ｂ高密度脂蛋白（ＨＤＬ）和低密度脂蛋白（ＬＤＬ）水平进行了测定，结果显示：（１）糖尿病患者Ａｐｏ－Ａｌ水平和Ａｐｏ－Ｂ水平均明显高于正常人（Ｐ＜０．０１）。（２）住院治疗前，糖尿病患者血清ＨＤＬ水平明显低于正常人（Ｐ＜０．０１）。（３）住院治疗期间糖尿病患者血清ＨＤＬ水平显著增高（Ｐ＜０．０１），而ＬＤＬ水平无明显改变（Ｐ＞０．０５）。     

Normal metabolism of apolipoprotein B100-containing lipoproteins despite qualitative abnormalities in type 1 diabetic men

Aims/hypothesis Type 1 diabetic subjects are at increased risk of cardiovascular disease and exhibit multiple qualitative abnormalities of apolipoprotein (apo) B100-containing lipoproteins. This stable isotope kinetic experiment was designed to study whether these abnormalities are associated with changes in the synthesis and fractional catabolic rates of VLDL-, IDL- and LDL-apoB100.Methods Using a bolus followed by a 16-h constant infusion of ¹³C-leucine, we performed a kinetic study in eight men with type 1 diabetes treated with a continuous subcutaneous insulin infusion administered by an external pump and in seven healthy men, in the fed state.Results The mean HbA₁c level in the type 1 diabetic patients was 8.00±1.48%. Plasma triglyceride, and total, LDL and HDL cholesterol levels were similar in patients and control subjects. VLDL were less triglyceride rich in type 1 diabetic patients than in control subjects (VLDL triglyceride : apoB 6.91±0.81 vs 8.29±1.24 mmol/g, p=0.05). Conversely, the IDL and LDL of the type 1 diabetic patients contained relatively higher levels of triglycerides (IDL triglycerides : apoB 2.16±0.36 vs 1.57±0.30 mmol/g, p<0.01; LDL triglycerides : apoB 0.27±0.06 vs 0.16±0.04 mmol/g, p<0.05). The apoB100 pool size, production and fractional catabolic rates in the two groups of subjects were similar for all lipoprotein fractions.Conclusions/interpretation Despite qualitative abnormalities, especially abnormalities of triglyceride content, the metabolism of apoB100-containing lipoproteins is not altered in type 1 diabetic men with fair glycaemic control with continuous subcutaneous insulin infusion. The high risk of atherosclerosis in these patients cannot be explained by kinetic abnormalities of apoB100-containing lipoproteins.     

Lipoprotein(a): Pathophysiology,measurement, indication and treatment in cardiovascular disease. A consensus statement from the Nouvelle Société Francophone d’Athérosclérose (NSFA)

Central Illustration. Pathophysiological pathways providing a causal link between high plasma concentrations of lipoprotein(a) (Lp(a)) and atherosclerotic vascular disease and aortic valve stenosis (AVS). Clinical outcomes are related to accelerated atherosclerosis complicated by atherothrombosis (myocardial infarction, stroke), peripheral artery disease (PAD) or aortic valve replacement (AVR) caused by valve calcification and aortic stenosis. Apo(a): apolipoprotein(a); LDL: low-density lipoprotein; OxPL: oxidized phospholipids; NSFA: Nouvelle Société Francophone d’Athérosclérose; SP: serine-protease domain; V: plasminogen kringle V (reproduced with permission).

     

冠心病患者脂蛋白脂酶活性和载脂蛋白C的变化及意义

观察３０例冠心病、２０例高脂血症患者的血脂含量、载脂蛋白Ｃ及血浆脂蛋白脂酶活性的变化，结果显示：高脂血症患者血浆脂蛋白ＣⅡ水平比正常人高４５．７２％，（Ｐ〈０．００１），且与血甘油三酯值呈明显正相关（ｒ＝０．５９９，Ｐ〈０．００１）；冠心病患者血浆脂蛋白酶性显著低于正常人（Ｐ〈０．０１）。提示：高脂血症患者血浆载脂蛋白ＣⅡ水升高可能是甘油三酯升高的重要原因，冠心病患者的血浆脂蛋白脂酶活性降低，可能     

Reduced plasticity and mild cognitive impairment-like deficits after entorhinal lesions in hAPP/APOE4 mice

Mild cognitive impairment (MCI) is a clinical condition that often precedes Alzheimer disease (AD). Compared with apolipoprotein E-ε3 (APOE3), the apolipoprotein E-ε4 (APOE4) allele is associated with an increased risk of developing MCI and spatial navigation impairments. In MCI, the entorhinal cortex (EC), which is the main innervation source of the dentate gyrus, displays partial neuronal loss. We show that bilateral partial EC lesions lead to marked spatial memory deficits and reduced synaptic density in the dentate gyrus of APOE4 mice compared with APOE3 mice. Genotype and lesion status did not affect the performance in non-navigational tasks. Thus, partial EC lesions in APOE4 mice were sufficient to induce severe spatial memory impairments and synaptic loss in the dentate gyrus. In addition, lesioned APOE4 mice showed no evidence of reactional increase in cholinergic terminals density as opposed to APOE3 mice, suggesting that APOE4 interferes with the ability of the cholinergic system to respond to EC input loss. These findings provide a possible mechanism underlying the aggravating effect of APOE4 on the cognitive outcome of MCI patients.     

ABO blood group in Amerindians from Brazilian Amazon

Background : The Parakanã is a group of Indians with cultural similarities to the extinct Tupi group. They are an isolated native population from East Brazilian Amazon. A number of different O alleles have been found at the blood group ABO locus in populations of several ethnic origins (Caucasians, Blacks, Amerindians). Aim : The present study describes the ABO blood group polymorphism gene of the Parakanã Indians. The Amerindian group was carefully selected for racial background. Subject and methods : The blood group polymorphism was analysed in genomic DNA from 62 Parakanã Indians. We determined the 261G deletion, the T646A and C771T mutations described in O 1variant and the G542A substitution, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Results : All Amerindians studied were homozygous for the 261G deletion. The frequencies of the T646A and C771T mutations in Parakanãs (0.65) were lower than that observed in Kayapo, Yanomama and Arara Indians (0.91) ( &#104 2 = 18.24; p-v < 0.001. The G542A substitution in Parakanãs was also lower (0.22) than in other tribes (0.42) ( &#104 2 = 9.73; p-v = 0.001). Conclusions : The different O alleles including the G542A mutation are not distributed homogeneously among all Amazonian Amerindians. Our results are in agreement with other genetic markers studied previously in Parakanã Indians, whose distinct genetic pattern differs from Europeans and even from other Amerindians.     

Effects of interactions between ApoE polymorphisms,alcohol consumption and obesity on age-related trends of blood pressure levels in postmenopausal women: The Bambuì cohort study of aging (1997–2008)

Objectives

To evaluate the effects of interactions between ApoE genotypes, alcohol consumption and obesity on the age-related trends of blood pressure (BP) levels in postmenopausal women.

Study design

A population-based prospective cohort study of all residents in Bambuì, south-eastern Brazil, aged 60 years or older. Repeated BP measurements were obtained in four waves from 851 women who underwent ApoE genotyping at baseline (88.3% of those enrolled), and multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. The few measurements (2.1%) made during hormone replacement therapy were excluded from the analysis.

Results

Alcohol consumption was associated with high levels of systolic and diastolic BP in an age × genotype-dependent manner only in the non-obese women (BMI < 27 kg/m²). Among those with the ?3/3 genotype, the differences in systolic and diastolic levels between drinkers and non-drinkers estimated at the age of 60 years were respectively 13.7 mmHg (p = 0.022) and 10.7 mmHg (p = 0.002), and disappeared in the older age groups, in which drinking was associated with systolic/diastolic hypertension if the non-obese women were ?4 carriers.

Conclusion

In non-obese postmenopausal women, alcohol consumption is associated with systolic and diastolic hypertension early in those with the ?3/3 ApoE genotype, and late in ?4 carriers. We hypothesize the mediation of androgen hormones and the influence of ApoE genotypes on age at natural menopause. A better understanding of these mechanisms may guide better preventive choices.     

人重组载脂蛋白E在大肠杆菌中的表达和纯化

用含有载脂蛋白EcDNA的PET32a原核表达载体转化大肠杆菌BL21（DE3），使之高效表达载脂蛋白E-thioredoxin融合蛋白，利用融合蛋白上的一段组氨酸序列，用镍离子亲合层析柱进行分离纯化。由于在载脂蛋白E和thioredoxin之间存在凝血酶的识别位点，用凝血酶消化后，经SephacrylS-300凝胶过滤得到人重组载脂蛋白E。用此方法可以从1L大肠杆菌培养液中纯化20-30mg高纯度的各种载脂蛋白E异构体和非自然存原突变体。方法简便，产量高，纯度达95%以上。     

载脂蛋白E基因多态性与高脂血症的相关性研究

选取１３３例高脂血症患者及１２２例正常对照人群，用多聚酶链反应方法快速鉴定其载脂蛋白Ｅ的基因型，结合血脂分析，研究载脂蛋白基因多态性与高脂血症的关系，结果表明，Ｅ３等位基因的分布频率在病例组中明显低于对照且，病例组中Ｅ４等位基因的分布频率明显高于对照组，表明Ｅ４等位基因与高脂血症显著相关。     

冠心病患者血清载脂蛋白A5的变化及其与血脂和脂蛋白的关系

目的探讨冠心病患者血清载脂蛋白A5的变化及其与血脂和脂蛋白的关系。方法测定冠心病患者和健康对照者的血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B100和血糖的水平,同时采用酶联免疫吸附法测定血清载脂蛋白A5水平。按所测指标水平将冠心病患者又分为高值组和正常值组,分析比较这些组间载脂蛋白A5的水平,并将载脂蛋白A5水平与这些指标做相关性分析。结果与正常对照组比较,冠心病组载脂蛋白A5水平明显降低(P<0.05);总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平均明显升高(P<0.01或P<0.05);而高密度脂蛋白胆固醇、载脂蛋白A1和载脂蛋白B100水平差异没有显著性(P>0.05)。高甘油三酯组和正常甘油三酯组载脂蛋白A5水平均明显低于对照组(P<0.01);而高甘油三酯组载脂蛋白A5又明显低于正常甘油三酯组(P<0.01)。载脂蛋白A5水平与甘油三酯水平呈显著负相关(P<0.01);载脂蛋白A5水平与胆固醇、低密度脂蛋白胆固醇和载脂蛋白B100水平有呈负相关的趋势,与高密度脂蛋白胆固醇、载脂蛋白A1和血糖水平有呈正相关的趋势,但均无统计学意义(P>0.05)。结论载脂蛋白A5水平降低可能是冠心病的危险因素。血清载脂蛋白A5水平与血清甘油三酯水平呈负相关,载脂蛋白A5可能是甘油三酯代谢的重要调节因子之一。