非诺贝特治疗高甘油三酯及高尿酸血症3例报道

非诺贝特与以往的降脂药相比 ,其降低血清脂质作用较强 [1] ,同时还有使血清尿酸下降的作用 [2 ]。本文报道 3例未曾用过降血脂药的血清甘油三酯 ( TG)升高及高尿酸血症患者应用非诺贝特后取得了良好的疗效。1　临床资料病例 1,男 ,4 3岁 ,健康。 1999年 8月体检发现血 TG升高并伴有高尿酸血症。经饮食及运动疗法无明显改善。于同年 10月始 ,服用非诺贝特片 ,每次150 mg,每日 1次 ,4个月后 TG水平由 332 mg/ dl降至 10 0 mg/ dl;血尿酸水平由 8.6mg/ dl降至 5.6mg/dl。以后略有升高 ,但继续用药情况下控制良好。病例 2 ,男 ,50岁。 1998…     

非诺贝特治疗脂肪肝肝功能异常者高甘油三酯血症的安全性

目的:探讨非诺贝特在肝功能异常的脂肪肝患者治疗高甘油三酯血症的安全性。方法:应用非诺贝特0.1,3次/d,治疗57例经血生化检测和B超检查明确的肝功能异常之脂肪肝患者共4周,观察其服药前、后之肝功能及血脂水平的变化。结果:57例患者中有2例服药后发现肝功能恶化而停服非诺贝特,停服后肝功能未进一步恶化;另有5例出现消化道不良反应但无肝功能恶化,故坚持服药至4周。55例服药前TG、ALT、AST分别为3.57±1.25mmol/L、131.48±49.51 IU/L、85.16±22.23 IU/L,服药后分别为l.58±0.47mmol/L、46.09±20.18 IU/L、40.31±14.05 IU/L,服药前、后存在极显著差异(P<0.01、P<0.001. P<0.001)。结论;在严密监测肝功能的基础上.非诺贝特可安全地用于治疗肝功能异常之脂肪肝患者。     

非诺贝特与高甘油三酯血症病人基质金属蛋白酶2活性

目的 观察高甘油三酯血症病人血管内皮依赖性舒张功能和血清基质金属蛋白酶2(Matrix metalloproteinase-2,MMP-2)含量及非诺贝特的影响.方法 高甘油三酯(triglyceride,TG)血症病人30例,TG超过1.7 mmol/L;健康体检者30例,观察血管内皮依赖性舒张功能.用酶联免疫吸附试验检测血清中MMP-2含量,观察非诺贝特口服剂量200 mg/d治疗8周对上述指标的影响.结果 高甘油三酯血症病人血管内皮依赖性舒张功能及血清中肿瘤坏死因子-α,MMP-2的浓度明显高于健康人(P＜0.01);用非诺贝特治疗后,病人血清中肿瘤坏死因子-α,MMP-2浓度较前下降,内皮依赖性舒张功能高于治疗前(P＜0.01).结论 高甘油三酯血症病人存在血管内皮舒张功能障碍;非诺贝特能显著改善高甘油三酯血症病人血管内皮依赖性舒张功能,其内皮保护作用可能与降低血清中MMP-2浓度有关.     

非诺贝特对高甘油三酯为主的代谢综合征的影响

目的观察非诺贝特对高甘油三酯为主的代谢综合征的影响.方法40例高甘油三酯为主的代谢综合征患者分成两组,对照组单纯饮食+运动治疗,试验组饮食+运动+非诺贝特治疗,8周后观察效果.结果两组患者的BMI、TG、HDL-C、FBG、2hPG、FINS、Homa-IR均有改善,试验组明显(P<0.05).结论非诺贝特对高甘油三酯为主的代谢综合征患者具有改善脂代谢,及胰岛素抵抗的作用.     

非诺贝特对高甘油三酯血症人群胰岛素抵抗和胰岛β细胞分泌功能的影响

目的观察非诺贝特对高甘油三酯(TG)血症人群的胰岛素抵抗和胰岛β细胞分泌功能的影响。方法正常糖耐量、高TG血症(TG≥12．3 mmol/L)患者12例(HTG组),予非诺贝特200 mg/d治疗3个月,于治疗前后应用高葡萄糖钳夹技术评价胰岛素敏感性和胰岛β细胞功能。并与正常糖耐量、正常血脂志愿者12名(NC组)进行比较。结果HTG组胰岛素敏感性指数(ISI)显著低于NC组;第一时相胰岛素分泌(1PH)稍低于NC组;第二时相胰岛素分泌(2PH)和最大胰岛素分泌(INS120-150)均明显高于NC组。HTG组非诺贝特治疗后,ISI较治疗前显著升高(18．35±1．76 vs 9．40±1．76,P＜0．01);1PH变化无统计学意义[(247．7±32．9)mIU/L vs (225．7±36．7)mIU/L,P=0．94];2PH和INS120-150较治疗前降低[分别为(73．2±9．0)mIU/L vs (106．0±11．3)mlU/L,p=0．014;(89．2±8．9)mIU/L vs (141．6±13．8) mIU/L,P=0．005]。结论非诺贝特调脂治疗能显著改善高TG血症人群的胰岛素抵抗及高葡萄糖钳夹试验中的胰岛素分泌。     

非诺贝特对胰岛素抵抗大鼠肝脏脂肪酸氧化的影响

目的观察自发胰岛素抵抗的OLETF大鼠肝脏脂肪酸氧化代谢的异常以及非诺贝特对其的影响。方法以8周龄LETO大鼠为正常对照,将同周龄OLETF大鼠随机分为未治疗组和治疗组[非诺贝特20ms／（kg·d）],于17周龄及30周龄分批处死动物,使用实时定量RT－PCR法测定肝脏组织脂肪酸氧化相关基因过氧化物酶体增生物激活受体－α（PPAR－α）、丙二酰辅酶A脱羧酶（MCD）、脂酰辅酶A氧化酶（AOX）mRNA的表达。结果与唧0大鼠相比,未治疗组8周龄大鼠首先出现糖负荷后2h游离脂肪酸（FFA）水平升高（P〈0．05）,17周龄出现空腹FFA以及血糖、胰岛素水平的升高;30周龄时肝脏组织PPAR-α、MCD、AOXmRNA表达均下调,甘油三酯含量升高（P均〈0．01）。治疗组空腹FFA水平明显降低,肝组织PPAR-α、MCD、AOXmRNA表达上调,肝组织甘油三酯含量下降（P均〈0．05）。结论非诺贝特可使OLETF大鼠肝脏脂肪含量下降,这可能与其降低血清FFA水平及上调肝脏组织与脂肪酸氧化相关酶的基因表达有关。     

非诺贝特对高甘油三酯合并低密度脂蛋白冠心病患者前列环素 …

观察冠心病合并高甘油三酯，低高速密度脂蛋白－胆固醇血症患者应用非诺贝特治疗后，其血清对前列环素生物活性的影响。方法 选择冠心病组和正常组各２０例，以ＰＧＩ２对二磷酸腺苷诱导的血小板聚集的抑制率作为ＰＧＩ２生物活性的指标，在冠心病组服用非诺特前及一个月后，比较两组患者的血清对ＰＧＩ２生物活性的影响及与血脂的关系。     

非诺贝特对高胆固醇血症兔体重及脂肪组织过氧化体增殖物激活受体表达的影响

目的 :观察非诺贝特短期干预对高胆固醇血症兔体重和皮下脂肪量的影响 ,并阐明其可能机制。方法 :10只新西兰大白兔给予高胆固醇饲料饲养 8周后 ,随机分为两组 :①高胆固醇组 :继续饲以高胆固醇饲料 4周 ;②治疗组 :在饲以高胆固醇饲料的基础上给予非诺贝特 (30mg·kg-1·d-1) ,共 4周。另选普通饮食 12周兔 (5只 )作为对照组。实验结束后 ,取皮下脂肪组织称量 ,并行前脂肪细胞培养 ,应用半定量逆转录多聚酶链式反应(RT PCR)测定脂肪组织和细胞PPARγ和PPARαmRNA的表达。结果 :高胆固醇组血清总胆固醇、低密度脂蛋白胆固醇水平明显高于对照组 (P <0 .0 1) ,非诺贝特干预 4周未对血脂产生影响 ,但能降低体重及皮下脂肪量(均P <0 .0 5 ) ,RT PCR结果显示高胆固醇组脂肪组织PPARγmRNA表达高于对照组 [(0 .5 75± 0 .14 )∶(0 .4 2 5± 0 .0 8) ,P <0 .0 5 ],非诺贝特能降低高胆固醇饲养兔脂肪组织PPARγmRNA表达 [(0 .4 78± 0 .11)∶(0 .5 75±0 .14 ) ,P >0 .0 5 ],并呈剂量依赖性的降低前脂肪细胞PPARγmRNA表达。 3组兔脂肪组织PPARαmRNA表达差异无统计学意义。结论 :非诺贝特独立于降脂作用外 ,能降低高胆固醇血症兔体重和皮下脂肪量 ,其机制之一可能与下调脂肪细胞PPARγmRNA表达有关。这一作用可     

非诺贝特对高脂大鼠肝脏PPAR-α基因表达及血清LPL活性的影响

将30只高脂模型大鼠随机分为高脂组、非诺贝特低剂量组(低剂量组)和非诺贝特高剂量组(高剂量组),后两组分别采用非诺贝特100 mg/kg,35 mg/kg灌胃1次/d,高脂组以生理盐水灌胃.4周后,测定各组血脂(TC、TG、LDL-C和HDL-C)及脂蛋白脂肪酶(LPL)活性;并采用RT-PCR法检测各组肝组织过氧化物酶体增殖物激活受体(PPAR-α)表达情况.结果:与正常值相比,高脂组血清TG、TC和LDL-C明显升高(P＜0.01);HDL-C明显降低(P＜0.01),非诺贝特高、低剂量组TC、TC和LDL-C均明显低于高脂组(P＜0.05或P＜0.01);而高剂量组HDL-C明显高于高脂组(P＜0.05),TG低于低剂量组(P＜0.05).高、低剂量组的血清LPL活性和肝PPAR-α/β.actin灰度比值明显高于高脂组(P＜0.01);高剂量组高于低剂量组(P＜0.01).认为非诺贝特可使血清LPL活性增加,并上调肝脏PPAR-α基因表达,且与剂量相关联,此可能为其降脂作用的机理.     

非诺贝特联合坎地沙坦治疗高血压合并高甘油三酯血症疗效观察

将44例高血压合并高甘油三酯（TG）血症患者随机分为A组15例、B组14例、C组15例,A组口服非诺贝特（100mg／次,3次／d＋安慰剂,B组口服非诺贝特（剂量同前）＋坎地沙坦8mg／d,C组口服坎地沙坦（剂量同前）＋安慰剂。三组均连续治疗2个月。观察血压、血脂及C反应蛋白（CRP）等指标变化。结果三组治疗后SBP、DBP、TG、TC、LDL-C、CRP水平均明显降低,而HDL-C水平明显增加,且B组疗效优于A、C组。认为非诺贝特联合坎地沙坦治疗高血压合并TG血症对于改善脂质谱、降低血压和炎症因子具有正向附加效应,可减少心血管事件的发生。     

微粒化非诺贝特对高三酰甘油血症患者血管内皮功能的作用

目的 :探讨微粒化非诺贝特对高三酰甘油血症患者血管内皮功能的作用。方法 :对 30例高三酰甘油血症患者 (口服微粒化非诺贝特 2 0 0mg/d治疗 4周前后 )和 30例正常人采用高分辨超声技术检测血流介导的和硝酸甘油介导的肱动脉舒张功能 ,并测定血浆内皮素 (ET)和血脂。结果 :①高三酰甘油血症组血流介导的肱动脉舒张反应较正常组明显减弱 [(2 .7± 2 .0 ) %∶(15 .0± 8.0 ) % ,P <0 .0 1],而两组对硝酸甘油的血管舒张反应差异无显著性意义 [(15 .0± 5 .0 ) %∶(16 .8± 9.0 ) % ,P >0 .0 5 ]。②高三酰甘油血症患者微粒化非诺贝特治疗后血流介导的肱动脉舒张显著改善 [(11.0± 9.0 ) % ,P <0 .0 1],而硝酸甘油介导的血管舒张较治疗前无明显改变[(16 .2± 6 .0 ) % ,P >0 .0 5 ]。③高三酰甘油血症患者血浆ET水平显著高于正常人 [(10 6 .2± 19.2 ) μg/L∶(72 .4± 14 .1) μg/L ,P <0 .0 1],微粒化非诺贝特治疗后血浆ET水平显著降低 [(82 .7± 15 .5 ) μg/L ,P <0 .0 1],血清三酰甘油明显降低 (P <0 .0 5 )。结论 :微粒化非诺贝特对高三酰甘油血症患者受损的血管内皮依赖性舒张功能有改善作用。改善血管内皮功能亦是微粒化非诺贝特防治冠心病的作用机制之一     

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.     

Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability

BACKGROUND: Epidemiologic investigations suggest that fish oil, which contains eicosapentaenoic acid (EPA), has favorable cardiovascular effects. Fish oil improves endothelial function in subjects with hypercholesterolemia or diabetes. However, controversy persists regarding relationships between primary hypertriglyceridemia and endothelial dysfunction. Moreover, lipoproteins are more susceptible to oxidation in vitro after incorporation of fish oil. METHODS: We determined the effects of EPA on serum lipids, susceptibility of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) to oxidation, and endothelial function in hypertriglyceridemic (HTG) subjects. In 8 men with untreated primary hypertriglyceridemia (plasma triglyceride between 150 and 500 mg/dL) and 7 control subjects (triglyceride below 150 mg/dL), forearm blood flow (FBF) responses were tested. In HTG subjects, this was repeated 3 months after initiation of EPA (1800 mg/day). Cu2+-induced oxidation of VLDL and LDL was determined by serial measurement of conjugated dienes. We used lag time, which corresponded to the period when the lipoproteins were resistant to oxidation, as a parameter of oxidizability. FBF responses to acetylcholine and sodium nitroprusside were determined by strain-gauge plethysmography. RESULTS: Plasma triglyceride in HTG subjects fell 31% with EPA supplementation. Before EPA, VLDL and LDL lag times in HTG subjects were shorter than in control subjects. EPA further reduced lag time for VLDL but not LDL. The FBF response to acetylcholine (but not to nitroprusside) was significantly less in HTG subjects before EPA than in control subjects. EPA normalized the FBF response to acetylcholine. CONCLUSIONS: EPA improves endothelial function in HTG subjects despite increasing in VLDL oxidizability.     

Apolipoproteins C-II and C-III metabolism in hypertriglyceridemic patients. Effect of a drastic triglyceride reduction by combined diet restriction and fenofibrate administration

Four hypertriglyceridemic patients, who had received an equilibrated high calorie diet and no lipid lowering drug for 1 month, were injected intravenously with 125I-apo C-II and 131I-apo C-III labeled homologous lipoproteins. Plasma and urine radioactivity, lipid and apolipoprotein levels were followed at regular intervals for 15 days. At the end of this first kinetic study the patients were advised to adhere for 1 month to a more restricted diet, limited in fat, and were given additionally 300 mg fenofibrate daily. After this treatment, a new kinetic study involving intravenous injection (similar to the first one) was performed. The protocols of both studies were identical. Treatment (diet plus drug) (1) reduced total cholesterol by 26 +/- 8%, triglycerides by 56 +/- 15%, apo C-II by 36 +/- 14%, and apo C-III by 48 +/- 10%; (2) modified the distribution of radioactivity between lipoproteins proportionally to the change in their mass ratio (decrease in VLDL and increase in HDL); (3) changed the kinetics of both apoproteins by rising the fractional removal rate, shortening residence time and decreasing the synthesis rate of both apolipoproteins C-II and C-III. The treatment was, however, unable to reduce the synthesis rate of apo C-III to normal, suggesting a major role of the apoprotein overproduction in the triggering of hypertriglyceridemia.     

缬沙坦对高血压患者血管内皮功能的影响

目的探讨高血压患者血管内皮功能的变化及缬沙坦对其影响。方法52例原发性高血压患者缬沙坦治疗8周与22例正常血压者对照,检测缬沙坦治疗前后血浆内皮素-1(ET-1)浓度,以及肱动脉超声检测血管内皮舒张功能的变化。结果(1)高血压组血浆ET-1明显高于对照组(P<0.01),缬沙坦治疗后明显下降(P<0.01)。(2)高血压组血流介导的肱动脉舒张低于对照组(P<0.01),缬沙坦治疗后明显改善(P<0.01)。结论高血压患者血管内皮功能受损,缬沙坦在降低血压的同时能改善血管内皮功能。     

Effect of atorvastatin on endothelial function in patients with familial hypercholesterolemia

AIM: To study the influence of treatment with HMG-CoA reductase inhibitor atorvastatin on endothelial function in patients with familial hypercholesterolemia type IIa. MATERIALS AND METHODS: Sixteen patients (5m/11w, 51-/+3 years) with familial hypercholesterolemia were studied before and after 3 months of therapy with atorvastatin 20 mg/day. EDRF release test (D.Celermajer, 1992) was used to assess flow-mediated endothelium-dependent vasodilatation (FMD) of the brachial artery in response to reactive hyperemia. Plasma nitrite/nitrate (NOx) levels were measured as an indirect index of nitric oxide (NO) production in vivo using HPLC. RESULTS: Atorvastatin treatment resulted in a 32% reduction in total serum cholesterol (CH), 41% reduction in low density lipoprotein (LDL) CH, 16% reduction in triglycerides and a 21% increase in high density lipoprotein CH. Flow mediated dilatation (FMD) was impaired at baseline (5.8-/+0.9%) and significantly improved up to 9.5-/+0.9% after 3 month atorvastatin therapy (p<0.002). Change in FMD inversely correlated with baseline FMD (r = -0.58, p<0.05). There was no significant correlation between FMD and neither total serum CH nor LDL CH levels at baseline. During atorvastatin therapy significant reduction of plasma NOx levels occurred from 53.4-/+5.1 mcmol/l at baseline (range 42.6-86.2 mcmol/l) to 35.5-/+5.1 mcmol/l (18.4-46.0 mcmol/l) after treatment (p<0.02, n=7). CONCLUSION: In patients with familial hypercholesterolemia atorvastatin produced beneficial effect on endothelial function (increase in flow-mediated dilatation, decrease in NOx).     

替米沙坦对代谢综合征患者血管内皮细胞功能的影响

目的:研究替米沙坦对代谢综合征患者的治疗作用及对血管内皮细胞功能的影响。方法:代谢综合征患者198例连续序贯分为替米沙坦组112例和生活方式干预组86例。治疗前后分别检测血压、空腹血糖、空腹胰岛素、血脂、一氧化氮、前列环素、内皮素-1、超氧化物歧化酶、丙二醛,超声检测内皮依赖性血流介导的血管舒张功能。结果:替米沙坦组和生活方式干预组患者治疗后结果分别与治疗前比较,血压、空腹血糖、空腹胰岛素、血脂、一氧化氮、前列环素、内皮素-1、超氧化物歧化酶、丙二醛均有明显改善(P<0.01),内皮依赖性血管舒张功能明显改善(P<0.01);与生活方式干预组患者治疗后的结果比较,替米沙坦组治疗后的血压、空腹血糖、空腹胰岛素、血脂、一氧化氮、前列环素、内皮素-1、超氧化物歧化酶、丙二醛的改善及内皮依赖性血流介导的血管舒张功能改善也有统计学意义(P<0.01)。结论:替米沙坦改善代谢综合征患者内皮依赖性血流介导的血管舒张功能,与其改善患者的胰岛素抵抗、血管内皮细胞的分泌功能及氧化应激反应有关。     

Effect of simvastatin on endothelial function in cardiac syndrome X patients

Patients with cardiac syndrome X with mild hypercholesterolemia were randomized to placebo (n = 20) or simvastatin 20 mg/day (n = 20). In the simvastatin group, there was a significant (26%; p < 0.0001) decrease in total cholesterol, a 38% (p < 0.0001) decrease in low-density lipoprotein cholesterol levels, and 7% a (p < 0.0001) increase in high-density lipoprotein cholesterol levels, without significant changes in triglyceride levels. Brachial artery flow-mediated dilation increased significantly (52% relative increase, p < 0.0001), and the time to > 1-mm ST-segment depression during stress testing was longer by the end of the study (p < 0.0001).     

法舒地尔对老年冠心病患者内皮祖细胞和内皮微颗粒数量及内皮功能的影响

目的研究法舒地尔对老年冠心病患者外周血中内皮祖细胞(EPC)、内皮微颗粒(EMP)以及内皮功能的影响。方法入选老年冠心病患者68例,随机分为法舒地尔组34例和对照组34例,2周后采用流式细胞技术检测2组患者在治疗前后EPC及EMP水平的变化,采用超声检测肱动脉介导内皮依赖性舒张功能(FMD)的方法,观察法舒地尔对老年冠心病患者血管内皮功能的影响。结果法舒地尔组与对照组治疗前EPC、EMP和FMD比较,差异无统计学意义(P>0.05)。与治疗前比较,治疗2周后法舒地尔组EPC和FMD较对照组明显升高,EMP较对照组明显降低,差异有统计学意义(P<0.05)。结论法舒地尔具有升高老年冠心病患者EPC数量、降低EMP水平和改善患者血管内皮功能的作用,法舒地尔治疗对老年冠心病患者的血管内皮功能具有保护作用。     

L-精氨酸对急性冠脉综合征患者血管内皮功能的影响

目的评价L-精氨酸对急性冠脉综合征患者血管内皮功能的影响。方法97例急性冠脉综合征患者被随机分到对照组、维生素C治疗组和L-精氨酸治疗组。所有患者分别于入院时及用药3周后取静脉血,测定血浆一氧化氮(NO)、内皮素-1(ET-1)、C-反应蛋白(CRP)和脂蛋白(a)[Lp(a)]的浓度。结果治疗3周后,L-精氨酸治疗组NO高于对照组(P<0.05),ET-1、CRP、Lp(a)低于对照组(P<0.01)。结论L-精氨酸能够改善急性冠脉综合征患者血管内皮功能。