微粒化非诺贝特对Ⅳ型高脂血症患者血清低密度脂蛋白亚组份再分布的作用

目的　观察微粒化非诺贝特对Ⅳ型高脂血症患者血清低密度脂蛋白亚组份再分布的作用。方法　口服微粒化非诺贝特2个月( 2 0 0mg ,每晚1粒) ,共治疗患者2 6例,对治疗后出现血清低密度脂蛋白-胆固醇水平升高15 %以上的共12例患者,进一步用超速离心法观察药物对血清低密度脂蛋白亚组份(LDL1 :1.0 2 5kg L～1.0 34kg L ,LDL2 :1.0 34kg L～1.0 44kg L)再分布的作用。结果　微粒化非诺贝特治疗后,血清甘油三酯水平平均下降5 3.4%～6 4.4% (P<0 .0 0 1) ,低密度脂蛋白-胆固醇明显升高37.3%～79.4% (P<0 .0 0 1) ,总胆固醇、高密度脂蛋白-胆固醇水平无明显改变。治疗前患者的低密度脂蛋白亚组份分布以小而密低密度脂蛋白3为主,LDL3 占总低密度脂蛋白的34.7%±8.6 % ,分布曲线呈多峰、不均一态分布;治疗后低密度脂蛋白3比例显著降低35 .0 %±2 7.3 % (P<0 .0 0 1) ,低密度脂蛋白2显著升高46 .9%±2 9.0 % (P<0 .0 1) ,低密度脂蛋白亚组份分布曲线转向单峰、较均一态分布。治疗后低密度脂蛋白颗粒的化学组成构成比( % )发生较大变动,其中甘油三酯的构成比显著降低(P<0 .0 1) ,胆固醇酯的构成比和蛋白质的构成比不同程度增高,游离胆固醇的构成比无明显变化。结论　微粒化非诺贝特能明显的降低Ⅳ型高脂血症患者血浆甘油三酯水平和升高部分患者的低密度脂蛋白-胆固醇水平,有使不正常低密度脂蛋白亚组份分布及组成趋向正常化分布的作用     

向来闰化非诺贝特对Ⅳ型高脂血症患者血清低密度脂蛋白亚 …

目的 观察微粒化非诺贝特对Ⅳ型高脂血症患者血清低密度脂蛋白（ＬＤＬ）亚组份再分布的作用。方法 口服微粒化非诺贝特２个月（２００ｍｇ,每晚１粒）,共治疗患者２６例,对治疗后出现血清ＬＤＬ－胆固醇水平升高１５％以上的共１２例２,进一步用超速离心法观察药物对血清ＬＤＬ亚组份（ＬＤＬ１：１．０２５ｇ／ｍｌ￣１．０３４ｇ／ｍｌ,ＬＤＬ２：１．０３４ｇ／ｍｌ￣１．０４４ｇ／ｍｌ和ＬＤＬ３：１．０４４ｇ／ｍｌ￣     

微粒化非诺贝特治疗高脂血症疗效评价

评价微粒化非诺贝特治疗高脂血症(Ⅱ_b型12例、Ⅳ型22例)的疗效及耐受性,服用微粒化非诺贝特200mg,每晚一次,观察8周,治疗前后比较,治疗8周后,Ⅱ_b型TC下降15％(P<0.05),Ⅱ_b和Ⅳ型TG分别下降55.5％、67.6％(P<0.01、P<0.01),尿酸下降31.9％。结论:微粒化非诺贝特治疗Ⅱ_b、Ⅳ型高脂血症有效,且有部分降低尿酸作用。     

微粒化非诺贝特治疗高脂血症疗效和耐受性

上海市多中心、开放性、自身比较，观察微粒化非诺贝特２００ｍｇ，每晚一次，治疗１３１例高脂血症病人４～８周的疗效和耐受性。男性７６例，女性５５例，平均年龄５６．２±９．７３岁，所属高血脂类型：Ⅱａ型２６例，Ⅱｂ型５３例，Ⅳ型５２例。治疗８周之后，Ⅱａ和Ⅱｂ型患者血清总胆固醇明显降低（平均降低２０％，Ｐ＜０．０１），Ⅱｂ和Ⅳ型患者血清甘油三酯明显降低（平均降低６０％～６３％，Ｐ＜０．０１），未出现严重不良反应，结论：微粒化非诺贝特特别适用于治疗Ⅱｂ和Ⅳ型高脂血症患者。４例合并有高尿酸血症者，治疗８周后，血尿酸平均降低５９％。     

微粒化非诺贝特与标准化非诺贝特对原发性高脂血症疗效及安全性比较

为了比较微粒化非诺贝特与标准化非诺贝特对原发性高脂血症的疗效和安全性，将68例原发性高脂血症患者分别进行治疗，微粒化非诺贝特级38例，200mg，每晚服一粒；标准化非诺贝特组30例，每日300mg，分3次服，疗程均为8周。疗程结束时两组服药前后自身比较，血清总胆固醇平均降低分别为22．5％与17．7％；甘油三酯平均降低分别为53．5％与42．2％；高密度脂蛋白-胆固醇平均升高分别为21．2％与17．9％；谷丙转氨酶前组平均降低6．8％，后组平均升高19．4％，表明：微粒化非诺贝特较标准化非诺贝特具有更好的调脂作用，且安全方便。     

微粒化非诺贝特对糖尿病性高脂血症的疗效观察

糖尿病患者合并高脂血症在临床上极为常见，高脂血症明显增高糖尿病患者心脑血管等并发症的发病率[1]。当糖尿病患者血糖得到有效控制时，脂质代谢紊乱可明显改善，但对那些脂质代谢未能恢复正常的糖尿病患者应及早给予治疗。微粒化非诺贝特作为苯氧芳酸类药物的新剂型（商品名     

安慰剂对照观察微粒化非诺贝特对高脂血症患者的临床疗效

安慰剂对照观察微粒化非诺贝特对高脂血症患者的临床疗效秦树存齐鹏张维强赵美玲董振南方品芳张锦林玉珍徐小曼李永昌方欣付蕾附表非诺贝特治疗前后血脂水平变化（ｍｍｏｌ／Ｌ，ｘ±ｓ）组别例数治疗前治疗前后差数及差数百分比治疗后４周治疗后８周ＴＣ非诺贝特组３０５...     

微粒化非诺贝特调脂疗效的评价

诺贝特作为降脂药物之一,因其疗效确切在国内外得到广泛应用。制剂改进成为微粒化的缓释新剂型后,其良好的胃肠道吸收、恒定的血药浓度,更显示出比普通剂型疗效好的优点。作者对３４例高脂血症患者服用微粒化非诺贝特８周的疗效给予评价。１对象和方法１．１对象本院门...     

微粒化非诺特治疗高脂血症疗效评价

评价微粒化非诺贝特治疗高脂血症的疗效及耐受性，服用微粒化非诺贝特２００ｍｇ，每晚一次，观察８周，治疗前后比较，治疗８周后，Ⅱｂ型ＴＣ下降１５％，Ⅱｂ和Ⅳ型ＴＧ分别下降５５．５％、６７．６％，尿酸下降３１．９％。结论：微粒化非诺贝特治疗ⅡｂⅣ型高脂血症有效，且有部分降低水酸作用。     

微粒化非诺贝特与吉非贝齐治疗高脂血症的比较

本文比较了微粒化非诺贝特（力平脂）２３例与吉非贝齐２０例治疗高脂血症的疗效。提示力平脂治疗血脂异常适用范围广、疗效确切、用药量少、副作用小。     

Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects

BACKGROUND: The metabolic syndrome (MS) is often accompanied by atherogenic dyslipidemia, which is characterized by elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), and elevated numbers of small, dense low-density lipoprotein (LDL) particles. HYPOTHESIS: It was hypothesized that a threshold exists for the circulating TG level needed to produce changes in LDL subclass distribution. METHODS: Hypertriglyceridemic (TG > or =300 and <1000 mg/dl) subjects with the MS were randomly assigned to placebo (n=50) or 130 mg/day of micronized fenofibrate-coated microgranules (n=96) for 8 weeks. RESULTS: In the overall analysis, fenofibrate treatment resulted in significant (p < 0.05) changes versus placebo in TG (-36.6%), non-HDL-C (-7.5%), very low-density lipoprotein-C (-32.7%), LDL-C (15.0%), HDL-C (14.0%), remnant lipoprotein-C (-35.1%), apolipoprotein B (-6.0%), apolipoprotein A-I (5.3%), and apolipoprotein C-III--29.7%). Changes in LDL particle diameter in the fenofibrate group were significantly inversely associated with the TG level achieved on treatment (p = 0.019). When individually matched for percent change in TG, subjects with on-treatment TG < 200 mg/dl, in contrast to those with on-treatment values > or =200 mg/dl, had significantly different median responses (p < 0.05) in LDL size (0.79 vs. -0.06 nm) and cholesterol carried by small (-35 vs. 21 mg/dl) and large (31 vs. 11 mg/dl) particles. CONCLUSION: These data support the view that a threshold exists below which the TG level must be lowered to produce shifts in LDL particle size.     

低密度脂蛋白亚型与冠状动脉病变程度的关系

目的评价Lipoprint Systerm检测的低密度脂蛋白亚型与冠状动脉病变程度的相关性。方法回顾性搜集冠心病患者139例,所有患者应用Lipoprint Systerm对低密度脂蛋白亚型进行定量分析,并行冠状动脉造影检查,计算病变血管支数及Gensini评分,比较血管三支病变组与简单病变组、Gensini评分高分患者与低分患者的临床特征及脂蛋白亚型的差异,通过Logistic回归分析低密度脂蛋白亚型与冠状动脉病变程度的相关性。结果与简单病变组比较,三支病变组低密度脂蛋白(LDL3)、小而密低密度脂蛋白(sdLDL)、sdLDL浓度百分比升高(P0.05),LDL1～2浓度百分比降低(P0.05)。三支病变组高血压、糖尿病比例高(P0.05)。Logistic回归分析显示高血压、糖尿病、糖化血红蛋白(HbA1c)、LDL3、sdLDL、sdLDL浓度百分比与三支血管病变呈正相关,LDL1～2浓度百分比与三支血管病变呈负相关。与Gensini低分组比较,Gensini高分组极低密度脂蛋白(VLDL)、总胆固醇(TC)、非高密度脂蛋白(nonHDL)、甘油三酯(TG)、LDL3、LDL4、LDL6、sdLDL、sdLDL浓度百分比升高(P0.05),LDL1～2浓度百分比降低(P0.05)。Logistic回归分析显示高血压、HbA1c、LDL6、LDL7、sdLDL、sdLDL浓度百分比与Gensini评分呈正相关,LDL1～2浓度百分比与Gensini评分呈负相关。结论 sdLDL及sdLDL浓度百分比与冠状动脉病变程度正相关,LDL1～2浓度百分比与冠状动脉病变程度负相关。     

Autoantibodies to oxidized low density lipoprotein: the relationship to low density lipoprotein fatty acid composition in diabetes

Autoantibodies to oxidized low density lipoprotein have been shown to be an independent predictor of the progression of carotid atherosclerosis. This study examines the relationship between low density lipoprotein fatty acid composition and autoantibodies to both malondialdehyde-modified and copper-oxidized low density lipoprotein in non-diabetic patients with (n = 17), and without (n = 18), definite evidence of previous myocardial infarction. The third group were non-insulin-dependent diabetic patients with no evidence of atherosclerosis (n = 15) and the fourth group were patients with non-insulin-dependent diabetes (n = 17) who had definite evidence of previous myocardial infarction. Fatty acids were measured by gas-liquid chromatography. Antibodies to malondialdehyde-modified low density lipoprotein and copper-oxidized low density lipoprotein were determined by an ELISA method. Autoantibodies to copper-oxidized low density lipoprotein were significantly higher in the non-diabetic patients with heart disease when compared to any other group (p < 0.05). Autoantibodies to malondialdehyde-modified low density lipoprotein were significantly higher in the non-diabetic subjects with heart disease and in both diabetic groups compared to non-diabetic subjects without coronary heart disease (p < 0.05). Lineolic acid (%) in low density lipoprotein did not differ between groups but arachidonic acid (%) was significantly lower in both diabetic and non-diabetic patients with coronary heart disease (p < 0.05). The diabetic patients with low antibodies had 39.6 ± 2.2 % polyunsaturated fatty acids in their low density lipoprotein while diabetic patients with high antibodies had 46.7 ± 1.2 % polyunsaturates in their low density lipoprotein (p < 0.01). This study confirms the association between antibodies to oxidized low density lipoprotein and coronary heart disease and shows raised low density lipoprotein antibody levels in diabetic patients with and without demonstrable atherosclerosis. In the diabetic patients, those with high antibody levels had high polyunsaturated fatty acid levels in their LDL suggesting a possible role for dietary intervention. © 1997 John Wiley & Sons, Ltd.     

成人低密度脂蛋白亚型与颈动脉内膜中膜厚度的关系

目的评价Lipoprint法检测的低密度脂蛋白(LDL)亚型对颈动脉内膜中膜厚度(CA-IMT)的预测价值。方法回顾性分析扬州大学附属医院心内科住院患者175例,平均年龄67岁,其中男性106例(60.6%),女性69例(39.4%)。所有患者应用Lipoprint脂蛋白分类检测系统对LDL细分类胆固醇及血脂四项定量分析,应用彩色多普勒超声检测仪测量颈总动脉内膜中膜厚度,分别比较传统危险因素下各分组间血脂水平及CA-IMT的差异。通过线性相关分析CA-IMT与传统危险因素及LDL各亚型的相关性,应用Logistic回归方法评估LDL亚型对CAIMT的预测价值。结果与男性比较,女性患者LDL4水平偏低(P0.05),CA-IMT低于男性(P0.01)。合并高血压及糖尿病等传统危险因素的患者小而密低密度脂蛋白(sd LDL)及其亚型、CA-IMT均高于正常对照组,但差异无统计学意义(P0.05)。相关分析显示CA-IMT与性别呈负相关(P0.05),与总胆固醇(TC)、LDL、非高密度脂蛋白(non-HDL)呈正相关(P0.05);与sd LDL及LDL亚型LDL3、LDL4呈显著正相关(P0.01)。CA-IMT还与传统危险因素吸烟呈正相关(P0.05)。Logistic回归分析显示LDL、sd LDL以及sd LDL亚型LDL3、LDL4为CA-IMT增厚的独立预测因素。结论 sd LDL及其亚型与CA-IMT相关,对动脉粥样硬化有预测价值。     

Metabolism by human endothelial cells of very low density lipoprotein subfractions isolated from Type 1 (insulin-dependent) diabetic patients

Summary The very low density lipoprotein (VLDL) fraction was isolated from 11 normolipidaemic Type 1 (insulin-dependent) diabetic patients in good to fair glycaemic control and from 11 age-, sex- and race-matched, non-diabetic, control subjects. The rate of receptor-mediated degradation by human endothelial cells was significantly greater (p<0.02) for the total VLDL fraction isolated from diabetic patients compared to control subjects and averaged 1008±300 and 717±150 ng·mg cell protein^–1·16 h^–1, respectively. The total VLDL fraction was separated into three subfractions: VLDL-I, S_f 100–400 (S_f = Svedberg units); VLDL-II, S_f 60–100; VLDL-III, S_f20–60. Rates of receptor-mediated degradation of VLDL-I and VLDL-II isolated from diabetic patients were significantly greater than the comparable subfraction isolated from control subjects and averaged 1023±279 vs 361±122 (p<0.01) and 433±70 vs 294±70 ng·mg cell protein^–1·16 h^–1 (p<0.03), respectively. Rates of receptor-mediated degradation of the V-III subfraction isolated from the two groups did not differ significantly. There were no significant differences in the chemical composition or in the plasma concentrations of the VLDL subfractions isolated from diabetic patients compared to control subjects. There was a significant increase in the apoprotein E content of VLDL-I (p<0.01) and VLDL-II (p<0.05) isolated from diabetic patients. There was a significant increase in the ratio of apoprotein C compared to apoprotein E (p<0.03) in VLDL-I isolated from control subjects compared to the diabetic patients. There were no significant differences in the apoprotein composition of VLDL-III isolated from the two groups.     

冠心病患者血浆小而密低密度脂蛋白的分布特征

目的观察冠心病患者血浆低密度脂蛋白(lowdensitylipoprotein,LDL)亚组分的分布特征。方法采用密度梯度超速离心法分离24例冠心病患者和13例对照组血浆中脂蛋白的各亚组分:大而轻LDL(LDL1),中间LDL(LDL2),小而密LDL(LDL3,)的含量。结果①冠心病组与对照组在年龄、性别、身高、体重、总胆固醇、甘油三酯、高密度脂蛋白胆固醇(highdensitylipoproteincholesterol,HDL-C)、载脂蛋白A(apolipoproteinA,ApoA)和载脂蛋白B(apolipoproteinB,ApoB)和LDL等指标差异均无统计学意义(P>0.05);②冠心病组的亚组分LDL1的含量少,LDL3的含量多;对照组则相反,亚组分LDL1的含量多,LDL3的含量小;而且两组差异有统计学意义。而介于两者之间的亚组分LDL2的含量两组几乎一样。结论LDL3与冠心病的发生、发展有关;LDL3测定仍可作为预测冠心病危险性的指标之一,也是观察疗效的指标之一。     

低密度脂蛋白对胰岛细胞功能的影响

目的探讨低密度脂蛋白（LDL）受体在胰岛β细胞（NIT-1细胞）上的表达及其LDL和氧化型LDL对胰岛β细胞功能的影响。方法实验室培养NIT-1细胞,用RT-PCR扩增后电泳检测LDL受体在NIT-1细胞上的表达;检测LDL及氧化型LDL对胰岛β细胞活性和胰岛素分泌及胰岛素mRNA表达的影响。结果LDL受体在NIT-1细胞上表达;与对照组相比,LDL及氧化型LDL对胰岛β细胞的活性无明显影响（P〉0．05）;LDL对胰岛β细胞胰岛素分泌无明显影响（P〉0．05）,氧化型LDL能显著抑制胰岛β细胞胰岛素的分泌（P〈0．01）;LDL对胰岛β细胞胰岛素mRNA表达无明显影响（P〉0．05）,氧化型LDL能显著抑制胰岛β细胞胰岛素mRNA表达（P〈0．01）。结论LDL受体在NIT-1细胞表达;LDL及氧化型LDL对胰岛β细胞活性无明显影响,但氧化型LDL显著降低胰岛β细胞胰岛素的分泌和细胞胰岛素mRNA的表达。     

糖化低密度脂蛋白与颈动脉粥样硬化的关系研究

目的　通过比较颈动脉粥样硬化患者与对照组之间的糖化低密度脂蛋白的血浆含量 ,寻找颈动脉粥样硬化与糖化低密度脂蛋白之间的关系。方法　颈动脉粥样硬化组 1 0 3例 (其中合并糖尿病组 47例 ,不合并糖尿病组 56例 ) ,对照组 43例。应用微柱亲和层析法分别测定两组糖化低密度脂蛋白的含量。结果　颈动脉粥样硬化组 (糖尿病组和非糖尿病组 )糖化低密度脂蛋白含量均较对照组明显增高 (P <0 .0 1 )。颈动脉粥样硬化造成动脉的狭窄程度与糖化低密度脂蛋白呈明显正相关 (r =0 .40 93 ,P <0 .0 1 )。非糖尿病合并颈动脉粥样硬化组的患者午餐后 2h血糖增高 ,同时胰岛素也明显增高 ,差异有显著性意义 (P <0 .0 5)。提示葡萄糖耐量异常和高胰岛素血症的存在。结论　糖化低密度脂蛋白在糖尿病和非糖尿病合并颈动脉粥样硬化发病方面均起重要的作用     

Effects of Acipimox on the metabolism of free fatty acids and very low density lipoprotein triglyceride

The mechanism of triglyceride lowering by Acipimox, a nicotinic acid analogue, was examined in a group of five moderately hypertriglyceridemic male rhesus monkeys. Two experiments were designed to examine the effect of the drug on lipid and glucose metabolism in nondiabetic, insulin-resistant animals. A single dose of Acipimox (8 mg/kg) given with a meal lowered the plasma free fatty acids (FFA) significantly at 4 h (0.102±0.008 vs 0.154±0.020 g/l; ±SEM;P<0.03); however, FFA concentrations returned to control levels at 6 h. Chronic administration of Acipimox (16 mg/kg q. i. d.) for 2 months produced a 31% reduction in triglyceride concentration (P<0.05) and a significant decrease in low density lipoprotein (LDL)-cholesterol (P<0.04), without changes in insulin action as measured by the hyperinsulinemic euglycemic clamp. Fasting FFA concentrations were not significantly altered by chronic treatment (0.163±0.013 versus 0.140±0.034 g/l). Fatty acid metabolic studies indicated increases in FFA transport (203.7±59.1 versus 136.1±26.6 μEq/min;P<0.05), while FFA fractional clearance rate (FCR) was unchanged. Very low density lipoprotein triglyceride (VLDL-Tg) metabolic experiments, using [³H]glycerol, showed increases in production and FCR with the drug. Increased VLDL-Tg clearance, in spite of increased production of VLDL, appears to be the mechanism by which triglycerides are lowered upon chronic Acipimox administration.