The Lipid-regulating Effects of Atorvastatin on Type 2 Elder Diabetes Patients with Hyperlipidemia

Inthisstudy,theeffectofatorvastatinonlipidmetabolism ,especiallysLDL ,intype 2elderdiabetespatientswithhyperlipidemiawasstudy .Theresultswerepresentedasfollows.1　SUBJECTSANDMETHODS1 1　SubjectsThesubjectsincluded 2 6patientswithtype 2elderdiabetesandhyp…     

阿托伐他汀对冠心病患者肱动脉内皮依赖性舒张功能的影响

目的：应用高频超声观察冠心病（CAD）患者，经阿托伐他汀治疗后对肱动脉内皮依赖性舒张功能（EDD）的改善作用。方法：经冠脉造影（CAG）确诊为CAD患者59例，利用高频超声血管技术检测阿托伐他汀对CAD患者治疗前后肱动脉EDD的疗效。结果：阿托伐他汀治疗2年后，EDD比治疗前有明显改善（P〈0．05），与对照组相比无显著性差异（P〉0．05）。常规治疗组治疗2年后，EDD无明显改善（P〉0．05），与阿托伐他汀组治疗后及对照组相比差异有显著性（P〈0．05）。结论：阿托伐他汀具有改善EDD的作用。     

阿托伐他汀治疗混合型高脂血症的疗效观察

目的　评价阿托伐他汀治疗混合型高脂血症的疗效。方法　将 6 2例高脂血症患者随机分为A、B两组 ,A组 32例 ,给予阿托伐他汀 10mg d,4周后血清胆固醇未下降 10 %者 ,可增量到 2 0mg d ;B组 30例 ,给予氟伐他汀2 0mg d,4周后血清胆固醇未下降 10 %者 ,可加量到 4 0mg d,两组均治疗 8周 ,观察降脂疗效。结果　阿托伐他汀组 ,总胆固醇 (TC)从 (6 83± 0 86 )mmol L降至 (4 6 8± 0 84 )mmol L ;甘油三酯 (TG)从 (3 16± 0 81)mmol L降至(2 0 4± 0 76 )mmol L ;低密度脂蛋白胆固醇 (LDL -C)从 (3 94± 1 2 2 )mmol L降至 (2 32± 0 77)mmol L (P均 <0 0 1)。两组降脂疗效间差别无显著性意义 (P >0 0 5 ) ,但治疗后两组患者的TG、LDL -C含量间差别有显著性意义(P <0 0 5 )。结论　阿托伐他汀有明显降TC、LDL -C、TG的作用 ,可用于混合型高脂血症的治疗     

Effects of atorvastatin on arterial endothelial function in coronary bypass surgery

Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 ± 1.8% vs coronary 4.1 ± 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.     

阿托伐他汀对系膜增殖性肾炎大鼠肾组织细胞外基质和纤溶酶原激活剂抑制物-1表达的影响

目的：观察阿托伐他汀对系膜增殖性肾炎（MsPGN）大鼠肾组织细胞外基质（ECM）和纤溶酶原激活剂抑制物-1（PAI-1）表达的影响，探讨其肾脏保护作用的机制。方法：采用抗胸腺细胞血清诱发的MsPGN大鼠模型，将SD大鼠随机分为正常对照组、肾炎模型组、小剂量阿托伐他汀治疗组（8mg·kg^-1·d^-1）和大剂量阿托伐他汀治疗组（16mg·kg^-1·d^-1）。治疗12d后。检测各组大鼠血总胆固醇（CHOL）、甘油三酯（TG）、血肌酐（Scr）和24h尿蛋白，以及肾组织Ⅳ型胶原（Col Ⅳ）、纤维结合蛋白（FN）和PAI-1的表达。结果：阿托伐他汀治疗组大鼠24h尿蛋白、肾组织Col Ⅳ、FN和PAI-1 mRNA的表达明显下降。肾组织病理改变明显改善，与模型组相比有统计学差异（P〈0．05），且呈剂量依赖关系。其中肾炎模型组尿蛋白（30．34±0．62）mg／d。阿托伐他汀小剂量治疗组（21．17±0．79）mg／d，大剂量治疗组（9．77±0．54）mg／d。同时，各组血脂水平无明显差异（P〉0．05）。结论：阿托伐他汀可显著改善MsPGN大鼠肾脏病变，抑制肾组织ECM成分和PAI-1的表达。     

Determination of the relative bioavailability of nedocromil sodium to the lung following inhalation using urinary excretion

Objective: To determine the effects of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Methods: Twelve healthy subjects participated in a randomized two-way crossover study. Each subject received atorvastatin 10 mg every morning for 2 weeks and atorvastatin 10 mg every morning with cimetidine 300 mg four times a day for 2 weeks, separated by a 4-week washout period. Steady-state pharmacokinetic parameters (based on an enzyme inhibition assay) and lipid responses were compared. Results: Pharmacokinetic parameters and lipid responses were similar following administration of atorvastatin alone and atorvastatin with cimetidine. Mean values for C_max (the maximum concentration) were 5.11 ng · eq · ml⁻¹ and 4.54 ng eq · ml⁻¹, for t_max (the time to reach maximum concentration) 2.2 h and 1.3 h, for AUC_0–24 (area under the concentration-time curve from time 0 h to 24 h) 58.6 ng eq · h · ml⁻¹ and 58.5 ng eq · h · ml⁻¹, and for t_1/2 (terminal half-life) 10.1 h and 17.0 h, respectively, following administration of atorvastatin alone and atorvastatin with cimetidine. Following treatment with atorvastatin alone and atorvastatin with cimetidine, mean values for the percentage change from baseline for total cholesterol were −29.5% and −29.9%, for low-density lipoprotein (LDL) cholesterol −41.0% and −42.6%, for high-density lipoprotein (HDL) cholesterol 6.3% and 5.8%, and for triglycerides −33.8% and −25.8%, respectively. Conclusions: The rate and extent of atorvastatin absorption and the effects of atorvastatin on LDL-cholesterol responses are not influenced by coadministration of cimetidine. Received: 17 February 1997 / Accepted in revised form: 3 November 1997     

ACAT-1 rs1044925单核苷酸多态性与急性冠脉综合征及阿托伐他汀治疗后血脂反应的关系研究

背景 既往研究显示ACAT-1 rs1044925单核苷酸多态性（SNP）与冠心病及缺血性脑卒中的发病风险相关,并且与血脂水平有关。目的 本研究旨在探讨ACAT-1 rs1044925 SNP与急性冠脉综合征（ACS）的关系,以及rs1044925 SNP与ACS患者阿托伐他汀治疗后调脂效果的关系。方法 选择2016年1月—2018年1月在广西壮族自治区人民医院老年心血管内科确诊为ACS并接受经皮冠状动脉介入治疗（PCI）的患者111例作为ACS组（男67例,女44例）;患者均接受阿托伐他汀治疗,20 mg/晚;同时服用氯吡格雷75 mg,1次/d（或替格瑞洛90 mg,2次/d）,阿司匹林100 mg,1次/d;并在经PCI后常规使用阿托伐他汀,20 mg/晚。对照组为同期体检健康人群,共338例（男170例,女168例）。通过聚合酶链反应和限制性片段长度多态性（PCR-RFLP）对ACAT-1 rs1044925 SNP进行基因分型,检测ACS组和对照组的基线血脂水平,随访检测ACS组患者阿托伐他汀治疗1年后血脂参数。结果 ACS组和对照组受检者的血清总胆固醇（TC）间差异无统计学...     

阿托伐他汀对Lewis大鼠实验性自身免疫性心肌炎作用的研究

目的： 探讨阿托伐他汀对实验性自身免疫性心肌炎(EAM）大鼠Th1/Th2偏离的影响及对EAM的治疗价值。方法: 6-8周雄性Lewis大鼠31只，其中8只作为正常对照；23只以猪心肌肌球蛋白免疫制成EAM模型，免疫后随机分为阿托伐他汀大剂量（10 mg·kg^-1·d^-1）组、小剂量（1 mg·kg^-1·d^-1）组和未治疗组，连续用药 21 d。第 21 d，行超声心动图检测；取心肌组织，观察大体及镜下炎症程度；ELISA检测血浆IL-2、IL-4、IL-10及IFN-γ等细胞因子水平,并以IFN-γ/IL-4比值作为Th1/Th2偏离方向指标。结果: 阿托伐他汀使EAM大鼠心室肥厚减轻，LVEDd降低，射血分数增加；心脏重量/体重比值及炎症程度分级显著降低；Th1型细胞因子(IFN-γ, IL-2)水平降低，Th2型细胞因子水平(IL-4, IL-10)升高。3组间TC、TG及HDL-C水平未见明显差异。结论: 阿托伐他汀使Th1/Th2平衡向Th1方向偏离，抑制EAM炎症反应。表明阿托伐他汀的免疫调节效应及在自身免疫病治疗中的应用前景。     

阿托伐他汀对自发性高血压大鼠心肌组织PPARs表达的影响

目的： 探讨阿托伐他汀对自发性高血压大鼠心肌组织PPARs（peroxisome proliferator-activated receptors, PPARs）表达的影响及其对心肌肥厚的逆转作用与可能机制。方法: 自发性高血压大鼠分为阿托伐他汀灌胃治疗组（SHR-A，30 mg·kg-1·d-1）及模型组（SHR），治疗8周，同周龄Wistar-Kyoto 鼠为正常血压对照组。治疗前及治疗后2、4、8周测量大鼠尾动脉血压。治疗后测血浆血脂水平，以心脏组织病理分析判断心肌肥厚，Western blotting 检测心肌组织PPARα、PPARγ的表达水平。结果: 经过8周治疗， SHR-A组及SHR组血压及血脂水平无明显差异（P＞0.05）。SHR-A组左室重量指数低于SHR组（P＜0.01）。在SHR-A组，PPARα及PPARγ表达高于SHR组（P＜0.01）。结论: 阿托伐他汀显著改善自发性高血压大鼠心肌组织PPARs表达，有效逆转左室肥厚，可能与其降压及降脂作用无关。     

不同剂量阿托伐他汀对急性冠脉综合征患者体内炎症反应、血小板活性及纤溶活性的影响

目的观察不同剂量阿托伐他汀对急性冠脉综合征(ACS)患者外周血中总胆固醇(TC)、高敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、血栓素B2(TXB2)、血小板颗粒膜蛋白-140(GMP-140)、血浆纤溶酶原激活剂抑制物-1(PAI-1)水平及血浆组织型纤溶酶原激活剂(t-PA)活性的影响。探讨阿托伐他汀对ACS防治的可能机制及不同剂量阿托伐他汀的安全性。方法ACS患者65例,在拜阿斯匹林、氯吡格雷等基础治疗外随机分为三组,分别给予阿托伐他汀10mg/d、20mg/d、40mg/d睡前服用。入院第1天、第14天分别抽取空腹静脉血16ml。测定hs-CRP、IL-6、TXB2、GMP-140、t-PA、PAI-1及TC、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、肌酸激酶(CK)。采用SPSS13.0统计软件对检测结果的组间及治疗前后进行比较。结果三组TC、hs-CRP、IL-6、TXB2、GMP-140、PAI-1治疗后均有下降、t-PA活性上升,治疗后三组间比较亦有差异;而三组治疗前后CK、ALT、AST组间无显著差异,治疗后无显著上升,以上结果均有统计学意义。结论阿托伐他汀对ACS患者血脂及炎症反应、血小板活性、纤溶活性有积极作用,并在一定范围内随着剂量的增加而加强,同时具有良好的安全性。