Clinical Assessment of Malondialdehyde-Modified LDL for Atherosclerotic Disorders

丙二醛修饰 LDL 治疗动脉粥样硬化性疾病的临床评估

• 批准号: 13557225
• 负责人: MAEKAWA Masato
• 金额: $ 8.96万
• 依托单位: HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557225/
• 关键词: Oxidized LDL; Malondialdehyde; Atherosclerosis; Diabetes Mellitus; Insulin; Statin; Fibrate; Anti-oxidation; 小粒子LDL; 中性脂肪; HDL; 高脂血症

1)Insulin treatment prevents LDL from accelerated oxidation in patients with diabetes.In a study population, we compared the level of malondialdehyde-modified LDL (MDA-LDL) with the concentrations of lipid parameteis in serum and found a strong correlation between MDA-LDL and apolipoprotein B (apo B) concentrations. Their interrelations had a turning point at an apo B concentration of 1,150 mg/l. In diabetic patients, the ratio of MDA-LDL/apo B increased at apo B concentrations above 1,150 mg/l. This ratio represents the extent of modification of apo B by MDA. In the control subjects, this ratio remained stable. When we divided the patients into medication groups (statins and insulin), we found that the 1,150 mg/l threshold disappeared. At apo B concentrations above 1,150 mg/l, the ratio of MDA-LDL/apo B in the stalin group was as high as that in the non-drug group. In the insulin group, the means of MDA-LDL/apo B in all ranges of apo B levels decreased to an extent statistically indis … More tinguishable from those of the control group. In conclusion, insulin therapy represses LDL oxidation even at apo B concentrations>1,150 mg/l and should be noted for its anti-oxidation properties.2)Influence of fibrate treatment on malondialdehyde-modified LDL concentration.Drug therapy is considered essential to the clinical prevention of atherosclerotic lesions in patients with diabetes mellitus (DM). To confirm the effects of fibrate therapy, we determined low-density lipoprotein (LDL) size by gradient gel electrophoresis and malondialdehyde-modified LDL (MDA-LDL) concentrations by enzyme-linked immunosolvent assay (ELISA) and clarified the association between apolipoprotein B (apo B) and MDA-LDL during the fibrate therapy. Mean MDA-LDL concentrations were higher in healthy men than in healthy women. There were no significant differences in mean MDA-LDL concentrations between age groups for males or females. According to the regression equation (y=0.063x+10.9) obtained for apo B and MDA-LDL concentrations with fibrate treatment, the apo B concentration in those may need to be decreased to 1260 mg/l to restore the MDA-LDL concentration to the control concentration (65 +/-25 units/l). This slope of the apoB/MDA-LDL regression line was approximately half of that with nd-drug treatment (y=0.109x-10.8). In conclusion, fibrate therapy had an effect on reducing serum MDA-LDL concentration in diabetic patients. Less

1)胰岛素治疗可防止糖尿病患者的低密度脂蛋白加速氧化。在一个研究人群中，我们比较了丙二醛修饰的低密度脂蛋白(MDA-LDL)水平和血清中脂质参数的浓度，发现丙二醛-低密度脂蛋白(MDA-LDL)和载脂蛋白B(Apo B)的浓度之间存在很强的相关性。在糖尿病患者中，当载脂蛋白B浓度高于1150 mg/L时，丙二醛-低密度脂蛋白/载脂蛋白B比值升高，这一比值代表了丙二醛对载脂蛋白B修饰的程度。在对照受试者中，这一比例保持稳定。当我们将患者分为他汀类药物组和胰岛素组时，我们发现1150 mg/L的阈值消失了。当载脂蛋白B浓度高于1150 mg/L时，斯大林组大鼠血清丙二醛-低密度脂蛋白/载脂蛋白B比值与非药物组相当。在胰岛素组，所有载脂蛋白B水平范围内的丙二醛-低密度脂蛋白/载脂蛋白B的平均值均有统计学意义上的下降，如…与对照组相比，更容易辨别。总之，胰岛素治疗即使在载脂蛋白B浓度为1150 mg/L的情况下也能抑制低密度脂蛋白的氧化，其抗氧化性能值得注意。2)贝特治疗对丙二醛修饰的低密度脂蛋白浓度的影响。药物治疗被认为是临床预防糖尿病患者动脉粥样硬化病变的关键。为证实贝特治疗的疗效，我们采用梯度凝胶电泳法测定低密度脂蛋白(LDL)的大小，用酶联免疫溶解试验(ELISA)测定丙二醛修饰的低密度脂蛋白(MDA-LDL)浓度，并明确载脂蛋白B(Apo B)与丙二醛修饰低密度脂蛋白(MDA-LDL)之间的关系。健康男性的平均丙二醛-低密度脂蛋白浓度高于健康女性。男性和女性的平均丙二醛-低密度脂蛋白浓度在各年龄组之间没有显著差异。根据贝特对载脂蛋白B和丙二醛-低密度脂蛋白浓度的回归方程(y=0.063x+10.9)，可能需要将载脂蛋白B浓度降至1260 mg/L，才能使丙二醛-低密度脂蛋白浓度恢复到对照浓度(65+/-25单位/L)。载脂蛋白B/丙二醛-低密度脂蛋白回归线的斜率约为ND药物治疗的一半(y=0.109x-10.8)。结论：贝特治疗可降低糖尿病患者血清丙二醛-低密度脂蛋白水平。较少

项目成果

近藤 明: "Relationship between Triglyceride Concentrations and LDL size Evaluated by Malondialdehyde-modified LDL"Clinical Chemistry. 47・5. 893-900 (2001)

Akira Kondo：“通过丙二醛修饰的 LDL 评估甘油三酯浓度与 LDL 大小之间的关系”临床化学 47・5（2001 年）。

近藤 明: "Relationship between HDL-cholesterol and malondialdehyde-modified LDL concentrations"J Atheroscler Thromb. (印刷中). (2003)

Akira Kondo：“HDL 胆固醇和丙二醛修饰的 LDL 浓度之间的关系”J Atheroscler Thromb（出版中）。

近藤 明, 他: "Relationship between HDL-cholesterol and malondialdehyde-modified LDL concentrations."J Atheroscler Thromb. 10. 72-78 (2003)

Akira Kondo 等人：“HDL 胆固醇与丙二醛修饰的 LDL 浓度之间的关系。”J Atheroscler Thromb。10. 72-78 (2003)

Kondo A, Maekawa M, Kanno T, Horli T: "Relationship between HDL-cholesterol and malondialdehyde-modified LDL concentrations."J Atheroscier Thromb. 10. 72-78 (2003)

Kondo A、Maekawa M、Kanno T、Horli T：“HDL 胆固醇与丙二醛修饰的 LDL 浓度之间的关系。”J Atheroscier Thromb。

Li J, 他: "A common truncated variant of lipoprotein lipase in the Japanese population is characterized by pattern B phenotype."Clin Chem Lab Med. 41(10). 1304-1307 (2003)

Li J 等人：“日本人群中脂蛋白脂肪酶的常见截短变体以 B 型表型为特征。”Clin Chem Lab Med 41(10) 1304-1307 (2003)。