氟伐他汀对实验性动脉粥样硬化家兔血脂及动脉粥样斑块的影响

目的：观察氟伐他汀对实验性动脉粥样硬化家兔血脂及动脉粥样块斑块的影响情况。方法：雄性新西兰白兔34只，体重2．0－2.5kg。随机分为四组：（1）正常对照组（n=7)：假手术＋正常饲料；（2）病理对照组（n=10）；动脉内膜剥脱术＋高脂饲料；（3）用药5周组（n＝7）：动脉内膜剥脱术＋高脂饲料＋4周后应用氟伐他汀5周（10mg.kg^-1.d^-1)。（4）用药9周组（n＝10）：动脉内膜剥脱术＋高脂饲料＋应用氟伐汀9周（10mg.kg^-1.d^-1）。观察实验各阶段各组家兔血脂及血管病理形态学变化。结果：实验前各组家兔血清脂质之间均无明显差别。实验9周时，两个用药组HDL浓度均显著高于两个对照组（P＜0．05）。病理结果显示两个用药组主动脉及髂动脉动脉粥样硬化程度明显轻于病理对照组。结论：氟伐他汀具有明显的降血脂及抑制动脉粥样硬化进展的作用。     

Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by nonsteroidal antiinflammatory drug

AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the ulceration in small intestines of rats. METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method. RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin) did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others (pravastatin, atorvastatin), CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.     

氟伐他汀对高脂餐后血浆甘油三酯和P-选择素浓度的影响

目的研究高血压病患者高脂餐后血浆P-选择素浓度变化,探讨氟伐他汀、或联合应用缬沙坦对血浆P-选择素浓度的短期影响。方法33例高血压病患者于禁食12h后接受高脂餐负荷试验(总热量800kcal,脂肪50g),检测空腹和餐后4h血浆甘油三酯(TG)、总胆固醇、低密度脂蛋白-胆固醇、高密度脂蛋白-胆固醇和P-选择素浓度。所有患者随机分为3组对照组、氟伐他汀组(40mg/d)和联合用药组(氟伐他汀40mg/d和缬沙坦80mg/d),1周后重复高脂餐负荷试验。结果3组患者具有相似的空腹血脂和P-选择素浓度。33例患者餐后血浆TG和P-选择素浓度较空腹水平明显升高(P<005),但3组间无明显差异。餐后血浆TG浓度与餐后血浆P-选择素浓度显著正相关(r=0427,P<005)。用药1周后,3组患者的空腹和餐后血浆TG浓度较基础状态无显著变化。对照组餐后血浆P-选择素浓度较空腹水平明显升高(P<005);氟伐他汀组与联合用药组能抑制餐后P-选择素升高;联合用药组更能明显地减少空腹血浆P-选择素浓度(P<005)。血浆P-选择素浓度的变化与治疗前后血浆血脂浓度和血压的变化无明显相关。结论短期内联合应用氟伐他汀和缬沙坦有效降低高血压病患者血浆P-选择素浓度,提示两药联合应用具有良好的协同作用。     

氟伐他汀、贝那普利单用及联用对稳定型心绞痛患者血浆同型半胱氨酸的影响

目的：探讨氟伐他汀、贝那普利单用及联用对稳定型心绞痛血浆同型半胱氨酸的影响。方法选择该院门诊及住院稳定型心绞痛患者血浆HCY〉15μmol/L 的120例患者,随机分为4组,常规治疗组：阿司匹林＋硝酸酯类药;氟伐他汀组：氟伐他汀（40 mg ,1次/d）＋常规治疗;贝那普利组：贝那普利（10 mg ,1次/d）＋常规治疗;联合治疗组：氟伐他汀（40 mg,1次/d）＋贝那普利（10 mg ,1次/d）＋常规治疗。治疗3个月后再次测定检测HCY。结果①血浆HCY〉15μmol/L 120例稳定型心绞痛患者中经治疗后,常规治疗组治疗前后差异无统计学意义（ P〉0.05）;氟伐他汀组、贝那普利组、联合治疗组治疗后血浆HCY水平显著降低,差异有统计学意义（ P〈0.01）;②氟伐他汀组与贝那普利组比较,差异无统计学意义（P〉0.05）;③联合治疗组与氟伐他汀组、贝那普利组比较,差异有统计学意义（P〈0.01）。结论氟伐他汀和贝那普利具有协同作用,两者都有降低稳定型心绞痛患者血浆中HCY水平的效能。     

两种不同他汀类药物对不稳定型心绞痛炎症因子影响比较

目的了解两种不同他汀类药物对不稳定型心绞痛患者的C-反应蛋白(hs-CRP),白介素-18(IL-18),基质蛋白酶-9(MMP-9)和血脂浓度的影响。方法选择2010年6月至2013年6月收治的60例不稳定型心绞痛患者作为研究对象。随机数字法分为两组,A组,30例,在常规治疗的基础上加用阿托伐他汀进行治疗;B组,30例,在常规治疗的基础上加用氟伐他汀进行治疗。测定并记录两组患者hs-CRP,IL-18,MMP-9,甘油三酯(TG),总胆固醇(TC),低密度脂蛋白-胆固醇(LDL-C),高密度脂蛋白-胆固醇(HDL-C),并进行对比分析。结果治疗后两组患者hs-CRP,IL-18,MMP-9均较治疗前显著降低,具有显著统计差异(P0.05),但组间治疗后水平无显著统计差异(P0.05);治疗后两组患者的TG,TC,LDL-C,HDL-C均较治疗前明显改善,具有显著统计差异(P0.05),组间治疗后比较,A组TC水平较B组降低更明显,其余指标TG、LDL-C和HDL-C下降程度相比无显著统计差异(P0.05);从不良反应发生率相比,两组在胃肠道症状和肝功能异常上相比具有显著统计差异(P0.05),而在急性冠状动脉病变上无显著统计差异(P0.05)。结论阿托伐他汀和氟伐他汀对降低不稳定型心绞痛患者的炎症反应和血脂均有一定疗效,虽然有不同程度的不良反应发生,但发生率都较低,在可控范围之内,因此两种他汀类药物是安全的,可靠的。     

Absorption and disposition of fluvastatin, an inhibitor of HMG-CoA reductase, in the rabbit.

The absorption and disposition of fluvastatin have been studied in the female rabbit. In naive rabbits receiving a single oral dose (1 mg kg-1) of [3H] fluvastatin, absorption was rapid and amounted to c. 90 per cent compared with an intravenous reference dose. The drug was subject to considerable first-pass effect, its absolute bioavailability being 46 per cent. The steady-state volume of distribution of fluvastatin was 0.29 +/- 0.04 l kg-1 while the total body clearance was 0.33 +/- 0.05 1 h-1 kg-1. The administered radioactivity was excreted predominantly in feces, with the renal pathway accounting for 28 +/- 4 per cent of the oral dose and 32 +/- 3 per cent of the intravenous dose. In pregnant rabbits on a multiple oral dosing regimen, 1 mg kg-1 day-1 beginning day 6 post-conception (p.c.), steady-state concentrations in maternal blood and tissues were achieved within 5 days. The concentrations in the reproductive organs were c. 25-50 per cent of that in maternal blood while those in the kidneys and liver were considerably higher. In contrast, radioactivity levels in the fetuses and amniotic fluid decreased significantly during repeated drug administration. The fetus: placenta and amniotic fluid: placenta concentration ratios declined from 0.92 and 0.97, respectively, on day 10 p.c. to 0.10 and 0.04, respectively, on day 18 p.c., indicating a limited transfer of fluvastatin and/or its metabolite(s) across the placenta at the later stage of pregnancy. After cessation of dosing, radioactivity levels in all tissues and fluids showed a progressive and nearly parallel decline, suggesting no tissue retention of the drug.     

氟伐他汀和普伐他汀治疗高脂血症的疗效比较(附78例报告)

目的:比较氟伐他汀和普伐他汀调整血脂的临床效果。方法:氟伐他汀组(40例,40mg,每日1次)和普伐他汀组(38例,20mg,每日1次)均连续服用4周。结果:两药降低血清总胆固醇,甘油三脂和升高HDL-C分别为87％和87％,60％和61％,65％和63％。结论:两药具有相近的调整血脂疗效。     

氟伐他汀防治支架术后再狭窄的临床试验

目的：探讨氟伐他汀对支架术后再狭窄的影响。方法：3个月后，应用多巴酚丁胺超声负荷试验(DSE)观察两组支架术后再狭窄的发生。结果：实验组再狭窄率9％，对照组21％。结论：氟伐他汀可以防止支架术后早期再狭窄的发生。     

氟伐他汀对兔髂动脉内皮剥脱后细胞增殖的影响

探讨氟伐他汀对兔髂动脉内皮剥脱后造成的动脉粥样硬化模型中细胞增殖的影响。将雄性新西兰兔随机分为氟伐他汀组 (n =2 8)和对照组 (n =2 8) ,用球囊导管剥脱内皮及高胆固醇饮食造成动脉粥样损伤 ,分别在内皮损伤后 1、2、4、8周处死动物并取髂动脉 ,用常规免疫组织化学染色和计算机图像分析方法观察氟伐他汀对新生内膜中平滑肌细胞增殖和血小板源生长因子 BB的影响。结果发现 ,氟伐他汀组内膜中增殖细胞核抗原染色阳性细胞率明显少于对照组 (P <0 .0 5 ) ;氟伐他汀组血小板源生长因子 BB含量一直处于较低水平 ,且明显低于对照组 (P <0 .0 5 ) ;血管内膜增殖细胞核抗原染色阳性细胞率与血小板衍生因子 BB含量的相关系数为 0 .712 7(P <0 .0 1)。提示氟伐他汀可能部分通过抑制血小板源生长因子 BB合成和分泌而抑制平滑肌细胞增殖。     

Towards standards for data exchange and integration and their impact on a public database such as CEBS (Chemical Effects in Biological Systems)

Integration, re-use and meta-analysis of high content study data, typical of DNA microarray studies, can increase its scientific utility. Access to study data and design parameters would enhance the mining of data integrated across studies. However, without standards for which data to include in exchange, and common exchange formats, publication of high content data is time-consuming and often prohibitive. The MGED Society (www.mged.org) was formed in response to the widespread publication of microarray data, and the recognition of the utility of data re-use for meta-analysis. The NIEHS has developed the Chemical Effects in Biological Systems (CEBS) database, which can manage and integrate study data and design from biological and biomedical studies. As community standards are developed for study data and metadata it will become increasingly straightforward to publish high content data in CEBS, where they will be available for meta-analysis. Different exchange formats for study data are being developed: Standard for Exchange of Nonclinical Data (SEND; www.cdisc.org); Tox-ML (www.Leadscope.com) and Simple Investigation Formatted Text (SIFT) from the NIEHS. Data integration can be done at the level of conclusions about responsive genes and phenotypes, and this workflow is supported by CEBS. CEBS also integrates raw and preprocessed data within a given platform. The utility and a method for integrating data within and across DNA microarray studies is shown in an example analysis using DrugMatrix data deposited in CEBS by Iconix Pharmaceuticals.