高脂血症患者血浆脂蛋白(a)免疫复合物测定的意义

目的研究高脂血症患者脂蛋白(a)[Lp(a)]-循环免疫复合物[Lp(a)-C IC]的水平与血浆脂质之间的关系。方法用酶法和酶联免疫分析分别测定38例男性高脂血症患者和38名正常对照者的血脂及Lp(a)-C IC。结果高脂血症患者的总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、Lp(a)和Lp(a)-C IC水平显著高于对照组,高密度脂蛋白胆固醇(HDL-C)低于对照组。血浆Lp(a)-C IC水平与LDL-C和Lp(a)浓度呈正相关,相关系数(r)分别为0.353(P=0.030)和0.735(P=0.000);Lp(a)-C IC与TG和HDL-C呈负相关,r分别为-0.433(P=0.007)和-0.346(P=0.030)。结论高脂血症患者体内存在高浓度的Lp(a)-C IC,其可能与该类人群易发粥样硬化有关。     

高脂血症患者血浆脂蛋白(a)免疫复合物测定的意义

目的 研究高脂血症患者脂蛋白（a）[Lp（a）]-循环免疫复合物[Lp（a）-CIC]的水平与血浆脂质之间的关系。方法 用酶法和酶联免疫分析分别测定38例男性高脂血症患者和38名正常对照者的血脂及Lp（a）-CIC。结果 高脂血症患者的总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、Lp（a）和Lp（a）-CIC水平显著高于对照组,高密度脂蛋白胆固醇（HDL-C）低于对照组。血浆Lp（a）-CIC水平与LDL-C和Lp（a）浓度呈正相关,相关系数（r）分别为0．353（P=0．030）和0．735（P=0．000）;Lp（a）-CIC与TG和HDL-C呈负相关,r分别为-0．433（P=0．007）和-0．346（P=0．030）。结论 高脂血症患者体内存在高浓度的Lp（a）-CIC,其可能与该类人群易发粥样硬化有关。     

脂蛋白(a)与动脉粥样硬化

高水平脂蛋白 (a) (Lp(a) )是动脉粥样硬化和血栓形成的独立危险因素。本文通过对Lp(a)的结构、功能及其与动脉粥样硬化之间关系的综述 ,分析讨论了Lp(a)致动脉粥样硬化的可能机制     

类风湿关节炎患者天然、氧化脂蛋白(a)水平

目的分析类风湿关节炎(RA)患者天然、氧化脂蛋白(a)[Lp(a)]水平及其与炎症的关系,探讨Lp(a)在RA患者心血管病发生中的意义。方法选择RA患者56例,其中活动性24例,非活动性32例;正常对照60例。对受检者天然、氧化Lp(a)水平以及炎症指标进行检测。结果活动性RA患者天然、氧化Lp(a)水平均高于非活动性RA患者和对照组,而非活动组和对照组间无变化。血沉和C反应蛋白均分别与天然、氧化Lp(a)呈正相关。结论RA患者天然、氧化Lp(a)水平发生显著变化,炎症反应对Lp(a)代谢具调节作用,参与动脉粥样硬化的发生、发展。     

脂蛋白(a)与动脉粥样硬化和血栓形成

脂蛋白 (a) [Lp(a) ]是动脉粥样硬化和血栓形成的独立危险因素。本文通过对Lp(a)的结构和理化特性及其与动脉粥样硬化和血栓形成之间的关系的综述 ,分析讨论了Lp(a)与动脉粥样硬化和血栓形成之间的可能机制 ,对全面认识Lp(a) ,真正揭示动脉粥样硬化血栓形成的发病机制 ,预防治疗心 ,脑血管疾病具有重要意义     

应用单克隆抗体的脂蛋白(a)免疫比浊测定

目的建立血清脂蛋白（ａ）［Ｌｐ（ａ）］单克隆抗体免疫比浊测定法。方法应用四株载脂蛋白（ａ）［ａｐｏ（ａ）］单克隆抗体，配制成全液体、双试剂，于自动分析仪二点反应法检测Ｌｐ（ａ）。结果检测试剂与纤维蛋白溶酶原和ａｐｏＢ无交叉反应，甘油三酯（１５ｍｍｏｌ／Ｌ）、胆红素（１５０μｍｏｌ／Ｌ）、血红蛋白（５００ｍｇ／Ｌ）对测定无干扰，检测范围０～１０００ｍｇ／Ｌ。该法与ＥＬＩＳＡ对照，结果无显著差异，ｒ＝０．９９。批内ＣＶ分别为２．５％［脂蛋白（ａ）７８５ｍｇ／Ｌ］和３．５％［脂蛋白（ａ）３００ｍｇ／Ｌ］，批间ＣＶ分别为３．９％和５．５％。结论ａｐｏ（ａ）单克隆抗体免疫比浊测定血清Ｌｐ（ａ）具有特异、灵敏、简便、快速和适用于自动分析等优点。     

脂蛋白(a)的测定方法与标准化研究近况

目前测定脂蛋白 (a) [Lp(a) ]的方法多为免疫化学方法 ,但由于Lp(a)结构的特殊性 ,使得不同方法、不同试剂之间结果缺乏可比性 ,需对测定方法进行优选与标准化。本文对其测定方法与标准化近况作一简述。     

血清低密度脂蛋白特异性循环免疫复合物的测定及其临床意义

为了建立血清低密度脂蛋白（ＬＤＬ）循环免疫复合物（ＬＤＬ－ＣＩＣ）的测定方法。利用酶联免疫吸附试验技术，以羊抗人ＩｇＧ作包板以识别ＣＩＣ中的抗体部分，以兔抗人ＬＤＬ作酶标物识别ＣＩＣ中的抗原部分。研究显示动脉粥样硬化病人血中的ＬＤＬ－ＣＩＣ明显高于对照组，ＬＤＬ－ＣＩＣ水平与血中ＬＤＬ以及其他修饰型ＬＤＬ含量无关。结果表明，该方法简便、稳定、ＬＤＬ－ＣＩＣ作为相对独立的危险因素参与了动脉粥样硬化的     

脂蛋白(a)与动脉粥样硬化

脂蛋白(a)[lipoprotein(a),Lp(a)]是动脉粥样硬化(atherosclerosis,AS)和血栓形成的独立危险因素。本文就Lp(a)的分子结构、遗传基础及其致AS、促血栓形成的可能机制作一综述。     

Lipoprotein (a) and its immune complexes in dyslipidemic subjects

OBJECTIVES: To investigate plasma levels of lipoprotein (a) [Lp(a)] and low-density lipoprotein (LDL)-circulating immune complexes (IC) in subjects with various dyslipidemias. METHODS: Plasma Lp(a), Lp(a)-IC, and LDL-IC levels were determined by enzyme-linked immunosorbent assays (ELISAs) in 198 subjects with various dyslipidemias and 34 control subjects. RESULTS: Hypertriglyceridemic subjects exhibited the lowest plasma Lp(a) levels, while hypercholesterolemic subjects exhibited the highest levels. Subjects with mixed hyperlipidemia had intermediate plasma Lp(a) concentrations, which were significantly lower than those of subjects with normal lipid levels. Interestingly, we also found that hypertriglyceridemic subjects had the lowest plasma Lp(a)-IC and LDL-IC levels, while hypercholesterolemic subjects exhibited the highest levels. Triglyceride (TG) levels were negatively correlated with Lp(a) (r = -0.15, P < 0.05), Lp(a)-IC (r = -0.20, P < 0.01), and LDL-IC (r = -0.214, P < 0.01) concentrations. Furthermore, significantly positive relationships were found between Lp(a)-IC and Lp(a) levels (r = 0.65, P < 0.001) and between LDL-IC and LDL-C levels (r = 0.43, P < 0.001). CONCLUSIONS: The results argue for a regulatory role of TG on plasma Lp(a) and its circulating immune complexes in subjects with various dyslipidemias. The circulating levels of these immune complexes levels are likely to change with different concentrations of Lp(a) and LDL.     

低能量氦氖激光血管内照射对高脂蛋白（a）的影响

目的　探讨低强度氦氖 (He Ne)激光血管内照射对高脂蛋白 (a) [Lp(a) ]患者的疗效。方法　将 40例Lp(a)升高的冠心病患者随机分为观察和对照组。两组条件和基础治疗相同 ,观察组加用低强度He Ne激光血管内照射 (ILIB)治疗 10d。结果　ILIB可降低人体内升高的Lp(a) ( P <0 .0 1) ,降低Lp(a)的有效率观察组显著高于对照组 (P <0 .0 5 ) ,并有升高HDL的倾向。对其他血脂成份及肝功、肾功、血糖均无显著影响 (P >0 .0 5 ) .观察组除 2例患者感头昏外 ,未发现其他副作用。结论　ILIB可降低人体内升高的Lp(a) ,是一种安全、有效的治疗方法 ,对冠心病的防治具有重要临床意义     

骨创伤患者血清脂蛋白（a）的变化及临床意义探讨

目的探讨骨创伤患者血清脂蛋白（a）[Lp（a）]的变化及临床意义。方法用免疫比浊法动态检测骨创伤患者（受伤24 h、72 h、1周、1个月）的血清Lp（a）水平,并与健康对照组和疾病对照组的血清Lp（a）水平作比较,观察骨创伤患者的血清Lp（a）的动态变化。结果12.5%的正常人血清Lp（a）水平超过300 mg/L,中位数（范围）为95.5（30.3-435.9）mg/L。受伤24 h、72 h、1周、1个月时采集静脉血,分别有33.3%、35.7%、38.1%、16.6%骨创伤患者的血清Lp（a）水平超过300 mg/L,中位数（范围）分别为145.5（36.3-1 260.8）、203.4（42.1-1 119.8）、164.9（39.0-1 007.6）、103.9（32.1-596.4）mg/L,受伤24 h、72 h、1周时骨创伤患者的血清Lp（a）水平明显高于对照组（P〈0.05）,1个月后骨创伤患者的血清Lp（a）水平基本恢复正常,与健康对照组比较无明显差异（P〉0.05）;疾病对照组中,术前有10%的患者血清Lp（a）水平超过300 mg/L,中位数（范围）为97.9（22.4-436.4）mg/L,术后24 h、72 h、1周、1个月时采集静脉血,分别有20%、30%、20%、15%手术患者的血清Lp（a）水平超过300 mg/L,中位数（范围）分别为142.9（26.9-800.1）、172.0（50.6-890.8）、143.9（39.8-808.1）、110.6（29.6-600.4）mg/L;疾病对照组与健康对照组相比,术后72 h的血清Lp（a）水平明显高于健康对照组（P〈0.05）,疾病对照组术后其余时段的血清Lp（a）水平与健康对照组比较无明显差异（P〉0.05）;疾病对照组术后与骨创伤组相同时段的血清Lp（a）水平比较无明显差异（P〉0.05）,但是疾病对照组术后的血清Lp（a）水平峰值低于骨创伤组。结论创伤患者的血清Lp（a）水平明显升高,约1个月后基本恢复正常,骨创伤患者的血清Lp（a）峰值高于疾病对照组术后的血清Lp（a）峰值。     

脑梗死患者血清脂蛋白（a）与C-反应蛋白检测的临床意义

目的探讨脂蛋白（a）与C-反应蛋白水平在急性脑梗死发病中的作用及临床意义。方法CRP水平由美国Beackman特定蛋白分析仪测定。脂蛋白（a）与血脂水平由美国Beackman全自动生化分析仪测定，同期测定30例健康体检者作为对照组并与之比较。结果脑梗死患者的血清脂蛋白（a）、C-反应蛋白水平显著高于对照组（P〈0．01），且脂蛋白（a）与CRP水平呈显著正相关（γ=0．710，P〈0．01）。结论①血清脂蛋白（a）是CRP水平升高的主要相关因素；②血清脂蛋白（a）和C反应蛋白含量的升高是脑梗死患者的危险因素。     

Detection of IgG-bound lipoprotein(a) immune complexes in patients with coronary heart disease

BACKGROUND: LDL-immune complexes (IC) have a powerful pathogenic role for inducing foam cell formation in vitro more efficiently than any other known mechanism. Studies have also shown that plasma LDL-IC concentration is a powerful marker for the development of atherosclerosis. The structure, fatty acid composition and antioxidant concentrations of Lp(a) and LDL are quite similar. The same oxidation pattern has also been described for both lipoproteins. Modified forms of Lp(a), some resembling oxidized Lp(a), have been identified in human atheromatous lesions. The existence of autoantibodies against MDA-Lp(a) in vivo is also presented. Therefore, we suppose that Lp(a) might trigger an immune response leading to the production of autoantibodies and subsequently to the formation of immune complexes. This study examined the existence of IgG-bound Lp(a)-IC and investigated its value as a risk factor for the development of atherosclerosis. METHODS: We developed two "sandwich" ELISAs for measuring plasma Lp(a)-IC and LDL-IC concentrations, using anti-human IgG(Fab) as the capture antibody, and quantitating with monoclonal anti-apo(a) or anti-apoB enzyme conjugate. Their concentrations were studied in 160 patients with coronary heart disease (CHD) and 290 control subjects. RESULTS: Plasma TC, LDL-C, TG and apoB concentrations in CHD patients were all significantly increased, whereas HDL-C and apoAI concentrations were decreased. The Lp(a) concentrations in the patients with CHD were also significantly different from those of control (262.4+/-220.0 vs. 211.3+/-199.4 mg/l, P<0.005). Plasma Lp(a)-IC (2.24+/-1.71 vs. 1.62+/-1.50 AU, P<0.0001) and LDL-IC (2.77+/-1.29 vs. 1.40+/-0.92 AU, P<0.0001) concentrations in patients with CHD were both significantly higher than those of control. The relationships between Lp(a)-IC, LDL-IC concentrations and other lipid traits in all the studied subjects (n=450) were carried out. LDL-IC concentrations were positively correlated with LDL-C, apoB, TC, TG and Lp(a) concentrations, while negatively correlated with HDL-C and apoAI concentrations, respectively. Similarly, Lp(a)-IC concentrations were positively correlated with Lp(a), LDL-C, apoB and TC concentrations, while negatively correlated with HDL-C and apoAI concentrations, respectively. Furthermore, a significantly positive relation between LDL-IC and Lp(a)-IC concentrations was also found (r=0.313, P<0.0001). CONCLUSIONS: We report the existence of Lp(a)-IC in both the plasma of patients with CHD and control subjects. Lp(a)-IC concentration increases in the CHD patients.     

肾病患者血清脂蛋白（a）中纤维蛋白溶酶原位点酶免疫测定意义

为了检测脂蛋白（ａ）〔Ｌｐ（ａ）〕中的纤维蛋白溶酶原（Ｐｇ）位点，建立了用单克隆抗载脂蛋白（ａ）为包被抗体，酶标抗Ｐｇ为检测抗体的双抗体夹心酶联免疫吸附法。慢性肾衰（ＣＲＦ）患者Ｌｐ（ａ）中Ｐｇ位点、Ｐｇ／Ｌｐ（ａ）比值较对照组显著升高。提示ＣＲＦ患者体内Ｌｐ（ａ）发生氧化修饰、合成增加导致Ｌｐ（ａ）同Ｐｇ同源性增加，更具致动脉粥样硬化发生的危险性。     

Lipoprotein(a): structural implications for pathophysiology

The assembly between a low-density lipoprotein particle and apolipoprotein(a), a highly carbohydraterich protein, gives origin to a peculiar class of lipoproteins, only found in the hedgehog, primates, and humans, termed lipoprotein(a). Apolipoprotein(a), which shares a high degree of sequence homology with the fibrinolytic proenzyme plasminogen, is linked to the apolipoprotein B-100 component of low-density lipoprotein via a disulfide bond and confers distinct biochemical and metabolic properties to lipoprotein(a). Because of its peculiar structural features and the observed correlation between high lipoprotein(a) levels and the development of a variety of atherosclerotic disorders, this lipoprotein has become the focus of an intense research effort. Although accumulation of lipoprotein(a) in the vessel wall at sites of vascular injury has been clearly evidenced, the mechanism(s) by which lipoprotein(a) exerts its pathogenic effect in this milieu remain largely unknown. It has been hypothesized that the pathological effect of lipoprotein(a) is related either to its similarity to low-density lipoprotein (i.e., a pro-atherogenic effect) or to the apolipoprotein(a) similarity to plasminogen (i.e., a pro-thrombotic/anti-fibrinolytic effect). However, it is probable that both components contribute to the pathogenicity of lipoprotein(a). The fact that lipoprotein(a) levels are largely genetically determined, varying widely among individuals and racial groups, adds additional elements to the scientific interest that surrounds this lipoprotein. Both clinical and biochemical studies of lipoprotein(a) have been complicated by the high degree of structural heterogeneity of apolipoprotein(a), which is considered the most polymorphic protein in human plasma. Our aim in this paper is to provide an overview of the most salient structural features of lipoprotein(a) and their possible pathophysiological implications.     

脂蛋白(a)循环免疫复合物诱导巨噬细胞胆固醇酯蓄积

目的探讨氧化、天然脂蛋白（a）[Lp（a）]循环免疫复合物（IC）致动脉粥样硬化作用。方法采用人源的氧化、天然Lp（a）与异源的抗载脂蛋白B（apoB）结合制备IC，观察不同浓度的Lp（a）-IC对小鼠腹腔巨噬细胞胆固醇酯的蓄积和泡沫细胞形成作用。结果氧化、天然Lp（a）-IC均引起巨噬细胞内胆固醇酯大量堆积，其效果强于Ox-Lp（a）（P〈0．001），且随着剂量的增加而升高，并转化为泡沫细胞；而天然Lp（a）、抗apoB处理的巨噬细胞内未见胆固醇酯的堆积。结论Lp（a）-IC导致巨噬细胞转化为泡沫细胞，参与动脉粥样硬化形成。     

Three different LDL apheresis columns efficiently and equally reduce lipoprotein(a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein(a) particles

Introduction

High levels of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] are associated with cardiovascular disease. In this study we determined apo(a) particle size and compared the Lp(a) reducing efficacy of three different LDL apheresis columns; DL-75, LA-15 and EC-50W in patients with familial hypercholesterolemia (FH).

Results

Average Lp(a) concentration was reduced by 70%, 74% and 75% (all p < 0.0001) for DL-75, LA-15 and EC-50W, respectively. No significant changes in the relative proportion of the isoforms of 14 and 32 K 4 domains were observed after apheresis.

Conclusion

Three different LDL apheresis columns reduced Lp(a) efficiently with preserved ratio between apo(a) isoforms.