血清ox-LDL/β2-GPI复合物在2型糖尿病合并冠心病中的作用研究

目的探讨血清氧化低密度脂蛋白(ox-LDL)/β2-糖蛋白Ⅰ(β2-GPI)复合物水平与2型糖尿病(T2DM)合并冠心病(CHD)的关系及其临床意义。方法选取T2DM合并CHD患者68例、单纯T2DM患者69例、单纯CHD患者65例、门诊健康体检者60名。用酶联免疫吸附试验(ELISA)检测血清ox-LDL/β2-GPI复合物水平,并测定空腹血糖(FBG)、总胆固醇(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)、糖化血红蛋白(HbA1C)和空腹血清胰岛素(FINS)、计算体重指数(BMI)及腰臀比(WHR),并作相关分析。结果 T2DM合并CHD组血清ox-LDL/β2-GPI复合物水平均显著高于单纯T2DM组、单纯CHD组和对照组,差异有统计学意义(P<0.05);T2DM合并CHD组ox-LDL/β2-GPI复合物水平均与TG和HOMA-IR呈正相关(r=0.219、0.228,P均<0.01);TG和ox-LDL/β2-GPI复合物是T2DM危险因素,ox-LDL/β2-GPI复合物和HbA1C是T2DM合并CHD的危险因素。结论血清ox-LDL/β2-GPI复合物与T2DM合并CHD的发病有一定联系。     

2型糖尿病肾病患者血清ox-LDL/β_2-GPI复合物水平的临床意义

目的探讨检测血清氧化的低密度脂蛋白/β2-糖蛋白I(ox-LDL/β2-GPI)复合物水平对2型糖尿病肾病(DN)的临床意义。方法以24 h尿蛋白排泄率(UAER)将76例DN患者分成3组,用酶联免疫吸附试验(ELISA)测定其血清ox-LDL/β2-GPI复合物水平,并以32名正常人作对照。结果血浆ox-LDL/β2-GPI水平与对照组比较差异有统计学意义(P<0.01),并且与尿白蛋白和胆固醇(TC)呈显著正相关(r=0.618,P<0.01)。结论 ox-LDL/β2-GPI对DN有较高的敏感性与特异性,提示其可能是DN的风险因素,也是较好的诊断指标。     

2型糖尿病肾病患者血清ox-LDL/β_2-GPI复合物水平的临床意义

目的探讨检测血清氧化的低密度脂蛋白/β2-糖蛋白I（ox-LDL/β2-GPI）复合物水平对2型糖尿病肾病（DN）的临床意义。方法以24 h尿蛋白排泄率（UAER）将76例DN患者分成3组,用酶联免疫吸附试验（ELISA）测定其血清ox-LDL/β2-GPI复合物水平,并以32名正常人作对照。结果血浆ox-LDL/β2-GPI水平与对照组比较差异有统计学意义（P〈0.01）,并且与尿白蛋白和胆固醇（TC）呈显著正相关（r=0.618,P〈0.01）。结论 ox-LDL/β2-GPI对DN有较高的敏感性与特异性,提示其可能是DN的风险因素,也是较好的诊断指标。     

2型糖尿病患者血清β2-GPI/ox-LDL复合物水平

目的 检测分析2型糖尿病(T2DM)患者血清β2-糖蛋白I/氧化低密度脂蛋白(β2-GPI/ox-LDL)复合物水平.方法 以抗人β2-GPI抗体为包被抗体、酶标记抗apo B为检测抗体的血清β2-GPl/ox-LDL ELISA检测法,对42例T2DM患者和41例年龄、性别匹配的健康对照者检测分析.用ELISA方法检...     

彩色多普勒超声评价血清氧化低密度脂蛋白/β2-糖蛋白Ⅰ水平对2型糖尿病肾病的影响

目的探讨应用彩色多普勒超声检查评价血清氧化低密度脂蛋白/β2-糖蛋白I(ox-LDL/β2-GPI)复合物水平对2型糖尿病肾病(DN)患者的影响。方法根据24h尿蛋白排泄率(UAER)将89例DN患者分成三组:A组(UAER<30mg/24h)、B组(UAER30～300mg/24h)和C组(UAER>300mg/24h),30例正常人作为D组对照。用酶联免疫吸附试验法测定其血清ox-LDL/β2-GPI复合物水平,并应用彩色多普勒超声仪检查四组受检者的肾脏血流灌注情况及肾脏各级动脉血流动力学参数。结果 B组、C组各级动脉的搏动指数(PI)、阻力指数(RI)均明显高于A、D组,差异均有统计学意义(t分别=1.96、2.02、2.14、2.58、2.07、2.22、2.51、2.76、2.18、2.32、2.66、2.84,P均<0.05),而收缩期最大血流速度(Vmax)、舒张期最低血流速度(Vmin)均明显低于A、D组,差异均有统计学意义(t分别=2.09、2.26、2.43、3.16、2.14、2.32、2.47、2.55、2.27、2.41、2.58、2.79,P均<0.05);C组各级动脉的Vmin均明显低于B组,而RI、PI则明显高于B组,差异均有统计学意义(t分别=1.73、1.99、1.81、2.07、1.95、2.13、1.76、2.32、2.09,P均<0.05);A、B、C三组血浆ox-LDL/β2-GPI水平均明显高于D组,差异均有统计学意义(t分别=2.81、3.35、3.97,P均<0.05),B、C两组血浆ox-LDL/β2-GPI水平均明显高于A组,C组血浆ox-LDL/β2-GPI水平明显高于B组,差异均有统计学意义(t分别=3.43、3.86、4.31,P均<0.05);ox-LDL/β2-GPI与B组及C组SRA的RI呈正相关(r=0.28、0.29,P均<0.05),且与B组及C组IRA的RI呈正相关(r=0.37、0.42,P均<0.05)。结论 ox-LDL/β2-GPI复合物水平与DN发病有关,应用彩色多普勒超声能够准确、快速检测DN患者的肾损伤。     

2型糖尿病微血管并发症患者血清miR-152，β2-GPI/ox-LDL和β2-GPⅠ-Lp(a)水平联合检测的价值研究

目的　探讨血清miR-152,β2-糖蛋白I氧化低密度脂蛋白复合物（β2-GPI/ox-LDL）和β2-糖蛋白I脂蛋白a复合物 [β2-GPⅠ-Lp(a)]水平联合检测对2型糖尿病（type 2 diabetes,T2DM）微血管并发症（type 2 diabetes associated microvascular complications,T2DMC）的诊断价值。方法　选取经临床确诊的T2DM患者79例,T2DMC患者78例及体检健康者78例,应用实时荧光定量PCR技术检测血清miR-152的水平,ELISA法检测血清β2-GPI/ox-LDL和β2-GPⅠ-Lp(a)水平,评价上述指标单独或联合检测对于T2DMC的诊断价值。结果　血清miR-152,β2-GPI/ox-LDL和β2-GPⅠ-Lp(a) 在T2DM患者中分别为44.99（25.71,77.97）fmol/L,0.574（0.376,1.040）U/ml和0.536（0.198, 1.056）U/ml,T2DMC患者分别为65.27（43.7,118.1）fmol/L,0.829（0.591,1.138）U/ml和0.597（0.186,1.139）U/ml,均高于健康对照组[13.68（8.14,21.63）fmol/L, 0.497（0.196,0.677）U/ml和0.156（0.078,0.476）U/ml],差异有统计学意义（U=616~2 192,均P< 0.05）。ROC曲线显示,血清miR-152,β2-GPI/ox-LDL和β2-GPⅠ-Lp(a)对T2DMC诊断的曲线下面积（AUC）分别为0.899（95% CI:0.847 ~ 0.950）,0.785（95% CI:0.716 ~ 0.855）和0.718（95% CI:0.637 ~ 0.798）;三者联合检测对T2DMC的AUC为0.963（95% CI:0.934 ~ 0.992）。Spearman秩相关分析显示,血清miR-152,β2-GPI/ox-LDL和β2-GPⅠ-Lp(a)组合与LDL水平呈正相关（r=0.188,P < 0.05）。结论　血清miR-152联合β2-GP1-ox-LDL,β2-GP1-Lp(a)对于T2DMC诊断具有较高的灵敏度和特异度,可有效弥补单指标检测不足,是T2DMC潜在的辅助诊断标志物。     

吗替麦考酚酯联合小剂量糖皮质激素对IgA肾病患者血清离子及β_2-糖蛋白I/氧化低密度脂蛋白复合物水平的影响

目的探讨吗替麦考酚酯联合小剂量糖皮质激素对IgA肾病血清离子及β_2-糖蛋白I/氧化低密度脂蛋白复合物(β_2-GPI/ox-LDL)水平的影响。方法选取IgA肾病患者68例,随机分为2组各34例。对照组在常规治疗基础上予以小剂量糖皮质激素治疗,研究组在常规治疗基础上予以吗替麦考酚酯联合小剂量糖皮质激素治疗。测定血清学指标,记录不良反应状况。结果 2组治疗后血磷及血清β_2-GPI/ox-LDL复合物水平显著降低,血钙水平显著升高,肌酐(Scr)、尿素氮(BUN)、血清胱抑素C(CysC)及24 h尿蛋白水平显著降低,血清转化生长因子β_1(TGF-β_1)、白细胞介素4(IL-4)水平显著降低,γ干扰素(IFN-γ)水平显著升高,血清基质金属蛋白酶-9(MMP-9)、血管内皮细胞生长因子(VEGF)、内皮素-1(ET-1)水平显著降低(P<0.05);与对照组比较,研究组治疗后血磷及β_2-GPI/ox-LDL水平显著较低,血钙水平显著较高,Scr、BUN、CysC及24 h尿蛋白水平显著较低,血清TGF-β_1、IL-4水平显著较低,IFN-γ水平显著较高,血清VEGF、ET-1和MMP-9水平显著较低(P<0.05)。结论吗替麦考酚酯联合小剂量糖皮质激素对IgA肾病疗效确切,能降低血清离子及β_2-GPI/ox-LDL水平。     

糖尿病患者血浆氧化、丙二醛修饰低密度脂蛋白及其自身抗体水平

目的探讨血浆氧化及丙二醛（MDA）修饰低密度脂蛋白（LDL）及其自身抗体与糖尿病（DM）及其他血脂项目之间的关系。方法选择DM患者、正常对照组各60例。采用酶联免疫吸附试验（ELISA）分别测定铜离子氧化型LDL（ox-LDL）、MDA修饰型LDL（MDA-LDL）及其自身抗体，同时对受检者血脂水平进行检测。结果DM患者血浆ox-LDL、MDA-LDL及其自身抗体水平均明显高于对照组（P〈0．01），分别与总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）呈高度正相关，而与高密度脂蛋白胆固醇（HDL-C）呈负相关；且ox-LDL、MDA-LDL分别同其自身抗体呈高度正相关。结论DM患者ox-LDL、MDA-LDL及其自身抗体水平显著升高，可能参与动脉粥样硬化的发生、发展过程。     

经皮冠状动脉介入治疗对血清β2-糖蛋白I/脂蛋白（a）复合物的影响

目的检测冠心病(coronary heart disease,CHD)患者血清β2-糖蛋白I/脂蛋白(a)[β2-GPI/Lp(a)]复合物水平,分析冠状动脉造影(coronary arteriongraphy,CAG)与经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术对其影响,并分析其临床意义。方法将患者分为2组:PCI组(CHD患者PCI术前、术后)与对照组(非CHD患者CAG术前),采用以抗人β2-GPI为包被抗体、酶标记抗载脂蛋白(a)为检测抗体建立的双抗体夹心酶联免疫吸附实验(ELISA),检测56例PCI组及30例对照组血清β2-GPI/Lp(a)复合物水平。结果 CHD患者PCI术后血清β2-GPI/Lp(a)复合物水平明显高于术前[(5.73±1.93)U/ml vs(3.08±1.64)U/ml,P<0.05]。结论 CHD患者血清β2-GPI/Lp(a)复合物水平于PCI术后明显升高,血清β2-GPI/Lp(a)复合物能作为反映机体氧化应激状态的一种潜在指标。     

冠心病患者血浆视黄醇结合蛋白与氧化低密度脂蛋白水平的相关性研究

摘要：目的：探讨冠心病患者血浆视黄醇结合蛋白（retinolbinding protein, RBP）水平与氧化低密度脂蛋白（oxidized lowdensity lipoprotein, ox-LDL）水平的相关性。 方法：分别采用免疫比浊法、ELISA法测定59例急性冠脉综合征（acute coronary syndrome, ACS）、62例稳定性冠心病（stable coronary artery disease, SCAD）患者和66例健康人（对照组）血浆RBP及oxLDL水平。 结果：ACS、SCAD患者RBP、ox-LDL水平显著高于对照组（P＜0.01）,而ACS组ox-LDL水平高于SCAD组（P＜0.01）。单因素分析显示血浆RBP分别与ox-LDL （r=0.312, P=0.001）和三酰甘油（TG）（r=0.251, P=0.006）水平呈正相关;ox-LDL分别与总胆固醇（TC）、TG、LDL-C相关。多元回归分析表明,冠心病患者血浆中RBP（β=0.260, P=0.018）、TG（β=0.496,P=0.000）及HDL-C（β=0.286, P=0.007）共同决定37.9%的ox-LDL水平变化。 结论：冠心病患者血浆RBP与ox-LDL水平相关。     

Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia

Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P相似文献   

Positive correlation between in vivo oxidized LDL and LDL immune complexes

OBJECTIVES: To investigate the possible relationship between oxidized low-density lipoprotein (ox-LDL) and LDL immune complexes (IC). METHODS: Both LDL-IC and ox-LDL were detected by sandwich ELISA. The levels were also studied in 60 patients with coronary heart disease (CHD) and 50 control subjects. RESULTS: Compared to controls, both the plasma ox-LDL concentrations (595.5 +/- 194.8 vs. 440.3 +/- 175.0 microg/l, P < 0.001) and LDL-IC levels (2.74 +/- 0.73 vs. 1.38 +/- 0.78 AU, P < 0.001) in the patients with CHD were significantly increased. The relationships between LDL-IC, ox-LDL levels, and other lipid parameters in all the studied subjects (n = 100) were analyzed. LDL-IC levels were positively correlated with TC, TG, LDL-C, lipoprotein(a) [Lp(a)], and apolipoprotein B (apoB) concentration, while negatively correlated with apoA1 concentration, respectively. Similarly, ox-LDL levels were also found positively correlated with TC, LDL-C, and apoB concentrations, respectively. Furthermore, a significantly positive correlation between ox-LDL and LDL-IC levels was found (r = 0.313, P < 0.005). CONCLUSION: In vivo oxidized LDL positively correlates with circulating levels of LDL immune complexes.     

Oxidized LDL in patients with coronary heart disease and normal subjects

Basic research has provided strong evidence that oxidation of LDL plays an important role in the progression of atherosclerotic vascular disease. The levels of plasma oxidized two-density lipoprotein (ox-LDL) were measured by sandwich ELISA using the monoclonal antibody (DLH3) recognized oxidatively modified lipoproteins and the anti-human apolipoprotein B monoclonal antibody in healthy subjects and patients with coronary heart disease (CHD). Plasma ox-LDL could be detected in normal subjects and patients with CHD. No sex-related difference was observed in normal subjects. The levels of ox-LDL in the forties and fifties were higher than those in the thirties and twenties. The levels of plasma ox-LDL were significantly higher in patients with CHD than in controls. There was no difference between the levels of ox-LDL of patients with single vessel disease and those with multivessel disease. These results suggest that elevated levels of oxidized LDL may be a marker for CHD.     

甲状腺功能亢进症患者血浆对氧磷酯酶1活性的测定

目的：探讨甲状腺功能亢进症（甲亢）患者血浆对氧磷酯酶1（PON1）活性变化以及与其它氧化应激指标的关系。方法：分别测定50名对照组和78例甲亢组空腹血浆中游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、PON1活性、超氧化物歧化酶（SOD）、丙二醛（MAD）、氧化低密度脂蛋白（ox-LDL）及血脂含量,并进行相关性分析。结果：甲亢患者血浆PON1活性（139±64）kU/L,ox-LDL（598.3±58.6）μg/L,MDA（15.11±3.26）μmol/L及SOD（80.2±25.3）NU/mL。对照组上述指标分别为：PON1（168±70）kU/L,ox-LDL（446.2±62.2）μg/L,MDA（10.02±3.00）μmol/L,SOD（92.9±26.9）NU/mL。血浆PON1和SOD活性显著低于对照组（P〈0.01）,ox-LDL和MDA水平显著高于对照组（P〈0.01）。甲亢患者血浆PON1活性与SOD呈正相关（r=0.381,P〈0.05）,与ox-LDL、MDA呈负相关（r=-0.411,r=-0.445,P〈0.01）。结论：甲亢患者血浆PON1活性显著降低,可能与氧化应激增强有关。     

Activity of myricetin and other plant-derived polyhydroxyl compounds in human LDL and human vascular endothelial cells against oxidative stress

Studies indicate that oxidative modifications of endothelium and LDL play a preeminent role in atherogenesis; therefore, the preservation of the endothelial antioxidant capacity and the inhibition of LDL oxidation by use of plant-derived compounds are an appealing strategy against several vascular disorders. On this basis, baicalein, eupatorin, galangin, magnolol, myricetin, oleuropein, silibinin and bilobalide were studied against various oxidative conditions. The radical scavenging capacity was analysed using DPPH and ORAC assays. Furthermore, the LDL oxidation was detected by measuring the formation of thiobarbituric acid reactive substances (TBARS) and by monitoring the oxidation kinetics. Further, we used cultured HUVEC to investigate the activities of the polyhydroxyl compounds towards the oxidative stress induced by H₂O₂. The lowest levels of TBARS were observed in the presence of oleuropein and baicalein, while myricetin, magnolol and eupatorin inhibited these ones to a lesser extent. In addition, oleuropein and myricetin exhibited higher protection in copper-induced LDL oxidation kinetics. However, only myricetin and galangin showed significant protective effects against H₂O₂ oxidative injury in HUVEC cells. Taken all together the results indicate myricetin as the most active agent among the selected plant-derived polyhydroxyl compounds, with prominent capacities against ox-LDL and ROS production in HUVEC.     

Facilitated nitration and oxidation of LDL in cigarette smokers

BACKGROUND: Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers. MATERIALS AND METHODS: Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion-exchange high-performance liquid chromatography (AE-HPLC) and measurements of thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine. RESULTS: Smokers showed a significantly higher level of TBARS and 8-OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3-nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption. CONCLUSION: The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.     

Plasma lipid composition and LDL oxidation.

Low-density lipoprotein (LDL) oxidation in vivo depends on lipid composition and on plasma antioxidant status. The aim of our study was to investigate the relationship between plasma lipid composition and LDL oxidation and, in particular, to explore whether LDL-cholesterol/triglycerides ratio (LDL-C/TG) and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio (LDL-C/HDL-C) can be used as predictive parameters of LDL oxidation in vivo. In 87 volunteers over a wide range of age plasma lipids and LDL oxidation were studied. Blood was collected after 12 h overnight fast. LDL oxidation was estimated by the level of conjugated diene (BDC) in the lipid fraction isolated from plasma after gradient ultra-centrifugation. The results were expressed as micromol/l (BDC/l) to evaluate the level of oxidized LDL, and as nmol of BDC for mg of LDL-cholesterol (BDC/LDL-C) for the evaluation of LDL oxidation degree. BDC/l correlated significantly with age, total and LDL-C, apolipoprotein B and TG, while BDC/LDL-C negatively correlated with total cholesterol, apolipoprotein B, LDL/TG and LDL/HDL ratios. Age of subjects significantly correlated with total and LDL-C and apolipoprotein B. TG have a significant inverse correlation with HDL-C. Our results support the hypothesis that among the several factors involved in LDL oxidation the most important determinants are LDL/TG. Plasma triglycerides appear to be very important even when circulating cholesterol levels are within normal limits. Moreover, we found that the LDL/HDL ratio is also very important with regard to the putative protective role of HDL against LDL oxidation in vivo. In conclusion, plasma lipid parameters must be evaluated not only for their absolute values but also for their mutual ratios as expression of plasma lipid homeostasis. Both LDL/TG and LDL/HDL ratios can be used as predictive parameters of in vivo LDL oxidation.