肾移植患者血脂,脂蛋白和载脂蛋白变化及其临床意义

观察了４６例肾移植患者血浆脂质代谢的改变，结果显示，肾移植患者血总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、极低密度脂蛋白胆固醇（ＶＬＤＬ－Ｃ）和载脂蛋白（ａｐｏ）Ｂ１００明显升高，而ａｐｏＡＩ、ａｐｏＡＩａｐｏＣⅡ／ａｐｏＣⅢ明显降低，同时还观察到，有心脑血管合并症的病者血ＴＣ、ＴＧ、ＴＣ／ＨＤＬ－ｃ、ａｐｏＢ１００升高ａｐｏＡＩ降低比合并症的病者更显著。上述结果表明肾移植后脂质代谢有明显改变，且存在加     

载脂蛋白B信号肽序列多态性及其与冠心病的关联

应用聚合链反应（ＰＣＲ）对１０３例冠心病人及１００名正常人载脂蛋白Ｂ（ａｐｏＢ）基因５＇端信号肽序列的多态性研究结果表明：（１）中国人信号肽序列插入／缺失（Ｉｎｓ／Ｄｅｌ）多态性频率分布与国外不同种族间有差异。少见Ｄｅｌ等位基因相对频率为０．２５９，高于南亚人，但低于法国高加索人。（２）冠心病组与正常对照组间等位基因相对组间等位基因相对频率分布差异无显著意义。（３）冠心病组内具Ｄｅｌ等位基因者血浆     

载脂蛋白A1、B基因多态性对非创伤性股骨头坏死发生的影响

目的:探讨载脂蛋白A1、B基因多态性对非刨伤性股骨头坏死(avascular necrosis of the femoral head,ANFH)发生的影响.方法:应用聚合酶链反应对中国北方汉族143例ANFH患者和92例正常人分别扩增含Apo AI基因启动子-75 bp和第一内舍子 83 bp及Apo B基因Eco RI、XbaI和3-VNTR的DNA片段,限制性内切酶酶切扩增产物,琼脂糖凝胶电泳分离基因多态性.结果:Apo A1基因启动子-75 bp处,ANFH患者中A/A基因型频率明显高于正常组(P＜0.01),而G/A基因型频率明显低于正常组(P＜0.01).Apo AI内舍子 83 bp位点,Apo B基因Eco RI、Xba I位点和3-VNTR区域ANFH患者组和正常组基因型及等位基因频率分布无统计学差异.结论:Apo A1基因启动子区域-75bp位点A/A型可能是非创伤性股骨头坏死易感基因之一,但未能发现Apo A1第一内舍子 83 bp位点及Apo B基因Eco RI、XbaI和3-VNTR位点多态性与非创伤性股骨头坏死发生有明显的关系.     

载脂蛋白A-Ⅰ对三磷酸腺苷结合盒转运体A1的影响

目的：以THP-1巨噬细胞源性泡沫细胞为研究对象，观察载脂蛋白A-I对THP-1巨噬细胞源性泡沫细胞胆固醇流出和三磷酸腺苷结合盒转运体A1(ABCA1)的影响,从而探讨载脂蛋白A-I对动脉粥样硬化(As)发生发展的影响。方法:用液体闪烁计数器检测细胞内胆固醇流出, 高效液相色谱分析细胞内总胆固醇、游离胆固醇和胆固醇酯含量, 运用逆转录-多聚酶链反应和Western 印迹分别检测ABCA1 mRNA 与ABCA1蛋白的表达,用流式细胞术检测细胞平均ABCA1荧光强度。 结果:载脂蛋白A-I引起THP-1巨噬细胞源性泡沫细胞总胆固醇、游离胆固醇与胆固醇酯呈时间依赖性减少, 而ABCA1蛋白质水平、细胞平均ABCA1荧光强度以及细胞内胆固醇流出呈时间依赖性增加,但ABCA1 mRNA没有明显变化。巯基蛋白酶抑制剂(leupeptin 和ALLN)增加ABCA1蛋白质水平,而其它蛋白酶抑制剂(pepstatin A、aprotinin及phosphoramiddon)不增加ABCA1蛋白质水平,蛋白体抑制剂(lactacytin)和溶酶体抑制剂(NH4Cl)也不影响ABCA1蛋白质水平。 结论:巯基蛋白酶可降解THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质,而载脂蛋白A-I可阻碍巯基蛋白酶降解ABCA1蛋白质,从而提高THP-1巨噬细胞源性泡沫细胞ABCA1 蛋白质水平, 增加细胞内胆固醇流出, 降低细胞内胆固醇聚积。     

载脂蛋白(a)5'调控区(TTTTA)n基因多态性与冠心病及其血清脂质的关系

目的:研究载脂蛋白(a)五核苷酸重复序列(PNR)基因多态性在湖北地区汉族人群冠心病(CHD)患者中的分布特点,进一步探讨其与血脂水平的关系。方法:采用聚合酶链反应结合聚丙烯酰胺凝胶电泳,分析了153例健康人及88例冠心病患者的apo(a)PNR基因型,并测定其血清胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、ApoAⅠ、ApoB及脂蛋白(a)的浓度进行分析。结果:CHD患者LP(a)、TC、TG、LDL-C水平明显高于对照组,HDL-C水平明显低于对照组(P<0.01);ApoAⅠ、ApoB两组间无显著差异;CHD组apo(a)PNR(TTTTA)_5/8基因型频率(0.181)和(TTTTA)₅等位基因频率(0.107)分别显著高于对照组(P＜0.05);(TTTTA)_5/8基因型者血清LP(a)水平高于(TTTTA)_8/8、(TTTTA)_8/9基因型者。结论:apo(a)PNR(TTTTA)₅等位基因可能是湖北地区汉族人群冠心病的危险因子之一。     

载脂蛋白E多态性与老年冠心病关系的临床研究

目的探讨人载脂蛋白E(apo E)遗传多态性与冠心病的关系.方法采用等电聚焦电泳及免疫印迹法测定102例正常老年人与91例老年冠心病人apoE表型,分析apoE表型与冠心病发病之间的关系.结果冠心病组与正常老年人组apoE表型与apoE等位基因频率分布无显著差异,均以E3/3表型常见和E3等位基因频率最高.结论apoE基因多态性在正常老年人及老年冠心病人之间比较无显著差异.     

Apolipoprotein genes and atherosclerosis

Summary In order to elucidate the genetic abnormalities underlying lipoprotein disorders associated with coronary heart disease susceptibility, researchers have looked for candidate genes. The studies have focused particularly on the lipoprotein transport genes. Relatively common as well as rare mutations have already been identified in several of these genes. In addition, further metabolic and genetic studies indicate that some of these loci harbor significant, but as yet undefined, genetic variation. In the next few years, it is not unreasonable to expect that all or most of the significant mutations at these loci will be catalogued. It is too early to know whether this will be sufficient to explain the genetic basis of altered lipoprotein levels or whether new loci will need to be investigated. Additional candidate gene loci might be those coding for genes involved in intracellular cholesterol metabolism, cholesterol absorption, or insulin resistance. New loci may also be revealed by the technique of reverse genetics. A more complete understanding of the genetics of atherosclerosis susceptibility will probably also entail the identification of variants at genetic loci that control both the reaction of the blood vessel wall to atherogenic lipoproteins and the thrombosis system. Investigation of the genetic basis of coronary heart disease susceptibility remains a worthwhile and lively field, with important clinical and public health ramifications.Abbreviations LPL lipoprotein lipase - HL hepatic lipase - LCAT ecithin cholesteryl acyltransferase - CETP cholesteryl ester transfer protein - RFLP restriction fragment length polymorphism - FCR fractional catabolic rate - HDL, LDL, VLDL, SDL high, low, very low, intermediate density lipoproteins     

Reflex testing I: algorithm for lipid and lipoprotein measurement in coronary heart disease risk assessment

We reviewed the current literature in order to construct a reflex testing algorithm that maximizes clinical utility and cost-effectiveness of lipid and lipoprotein testing. The algorithm was based on the 2nd Report of the National Cholesterol Education Program Adult Treatment Panel guidelines for use of total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C, and published reports describing the clinical use of apolipoprotein B and lipoprotein (a). The success of this algorithm was tested in a low-risk general and a high-risk hyperlipidemic patient population. Lipid data and non-lipid risk factors were obtained from a national database and from patients seen at two lipid clinics. A total of 16 968 individuals from the National Health and Nutrition Examination Survey III database comprised the low-risk group, and 239 patients examined in the Hartford Hospital and Washington University Lipid Clinics comprised the high-risk group. We found a solid scientific base to support the NCEP guidelines and reasonable support for limited testing of apoB and Lp(a). According to the algorithm, the direct LDL-C assay was deemed unnecessary in 98% and 91% of low- and high-risk subjects, respectively, if one assumes that the Friedewald equation is adequate with TG≤4.00 g/l. With a more conservative cutoff of TG≤2.50 g/l, the algorithm canceled 92% and 81% of direct LDL tests, respectively. The algorithm also limited TG to 20 and 64%, apoB to 6 and 20%, and Lp(a) to 15 and 56%, of low- and high-risk groups, respectively. Use of a comprehensive, reflex algorithm for coronary heart disease risk assessment will substantially reduce the utilization of laboratory services without diminishing the clinical value of these tests. The algorithm will prevent the overuse of certain expensive tests (direct LDL) while promoting the limited use of underutilized tests [apoB and Lp(a)].     

CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese

Cholesteryl ester transfer protein (CETP) is one of the factors that regulate plasma levels of HDL-cholesterol. To identify the factors that may regulate CETP activity, and to determine to what extent CETP is correlated with physiologic concentrations of lipoprotein, we performed an epidemiologic study in 586 healthy volunteers (317 males and 269 females, mean age 52.2 ± 10.9 years). CETP activity in these subjects was 192.96 ± 48.73 (mean ± S.D.) nmol/ml/h and distributed to a wide range (60–450 nmol/ml/h). Using multiple regression analysis, we found significant positive correlations between CETP activity and LDL-cholesterol (P < 0.03), apolipoprotein (apo) E (P < 0.005) and LCAT activity (P < 0.001). CETP activities showed significant negative correlation with apo A-I (P < 0.03). However, CETP activity showed no significant correlation either with HDL cholesterol or with apo B. One-way layout analysis of variance showed that alcohol drinking and cigarette smoking significantly reduced CETP activity, but there was no significant association between CETP activity and body mass index. Although CETP activities were significantly higher in females than in males (P < 0.001), multiple regression analysis showed no correlation between CETP activity and age in either the males or the females. Our results suggest that CETP activity regulates the concentration of apo A-I and LDL-cholesterol, and that such activity may be influenced by gender, alcohol consumption and cigarette smoking.     

冠心病患者载脂蛋白A5与脂联素和空腹胰岛素的关系研究

目的 探讨冠心病患者血清载脂蛋白A5(APOA5)与脂联素和空腹胰岛素(FINS)之间的关系.方法 检测2005年6月至12月在中南大学湘雅二医院心内科住院确诊的51例冠心病患者和同期在此院门诊进行健康体检的44名健康对照者血清APOA5、脂联素、FINS和血脂,并计算胰岛素抵抗指数(HOMA-IR).结果 冠心病组血清APOA5和脂联素显著低于健康对照组[(230.06±115.80)μg/L对(324.43±151.79)μg/L,(3.03±1.85)mg/L对(4.12±2.48)mg/L,P均＜0.05];冠心病组的FINS显著高于对照组[(9.85±5.94)mU/L对(7.85±3.04)mU/L,P＜0.05].APOA5与三酰甘油(TG)、FINS、HOMA-IR呈负相关,与高密度脂蛋白胆固醇(HDL-C)呈正相关,与脂联素不相关.结论 冠心病患者血清APOA5和脂联素降低,FINS增高.APOA5不但影响血脂代谢,而且可能与胰岛素抵抗有关.