阿托伐他汀对不稳定性心绞痛PCI术后炎症因子的影响

目的研究阿托伐他汀强化治疗对不稳定性心绞痛患者经皮冠状动脉介入术后高敏C-反应蛋白、肿瘤坏死因子α-和白细胞介素-6及血脂水平的影响。方法选择2007年10月～2008年4月在我院行PCI术的60例不稳定性心绞痛患者为研究对象，随机分为三组：常规治疗组（20例）：常规药物治疗；阿托伐他汀治疗组：在常规治疗基础上分别加用20mg（20例）和80mg（20例）阿托伐他汀治疗3d。分别于药物治疗前、药物治疗后3a（术前当天）及术后24h采集空腹静脉血，测定血清hs—CRP、TNFα、IL-6和血脂浓度。结果（1）常规治疗组与20mg阿托伐他汀组血清hs—CRP、TNFα．和IL-6浓度治疗3d后均没有显著性变化，而在PCI术后则均有显著性升高（P〈0．05）。（2）80mg阿托伐他汀治疗组治疗3d后hs—CRP、TNFα．和IL-6浓度均呈明显降低（P〈0．05），且经PCI术后亦无显著性升高。（3）三组治疗前、后的各血脂成份的变化差异均无显著性（P〉0．05）。结论PCI术可以导致血清hs—CRP、TNFα．和IL-6水平升高；阿托伐他汀（80mg）强化治疗3d后可明显控制PCI术后血清hs—CRP、TNFα．和IL-6水平的上升，从而减少心血管事件的发生。     

阿托伐他汀对急性冠脉综合征患者血浆纤维蛋白原和C反应蛋白的影响

目的：观察阿托伐他汀治疗对于急性冠脉综合征患者血浆纤维蛋白原和c反应蛋白的影响。方法：本试验采用前瞻性开放性病例对照研究，将84例急性冠脉综合征患者随机分为2组：A组（41例）采用常规治疗；B组（43例）在常规药物治疗基础上，加用阿托伐他汀（20mg／d）治疗，在治疗前以及治疗2个月后检测患者血浆纤维蛋白原及超敏C反应蛋白水平。结果：常规治疗对血浆纤维蛋白原和超敏c反应蛋白水平无明显影响；阿托伐他汀不但能降低血浆纤维蛋白原水平，还显著降低c反应蛋白水平。结论：阿托伐他汀改善急性冠脉综合征患者血液流变学，并具有抗炎作用，对于抑制心肌缺血的进展具有良好作用。     

强化降脂治疗老年不稳定型心绞痛临床观察

目的探讨强化降脂治疗老年人不稳定型心绞痛的疗效及安全性。方法选择76例老年不稳定型心绞痛患者，随机分为强化降脂组和普通降脂组进行疗效比较。普通降脂组常规服用阿斯匹林、硝酸盐类、β-受体阻滞剂、钙通道拮抗剂，另口服阿托伐他汀10mg。强化降脂组在常规治疗的基础上口服阿托伐他汀40mg。结果2组患者用药后，ST段压低数值总和（∑ST）均较用药前下降，强化降脂组心绞痛发作次数减少（P〈0．01），未见强烈副作用。心脏事件在普通降脂组也出现降低，但差异无统计学意义（P〉0．05）。结论强化降脂对协助控制老年不稳定型心绞痛患者心绞痛发作安全可靠，有一定疗效。     

Atorvastatin Transport in the Caco-2 Cell Model: Contributions of P-Glycoprotein and the Proton-Monocarboxylic Acid Co-Transporter

Purpose. The purpose of this study was to elucidate the mechanismsby which an HMG-CoA reductase inhibitor, atorvastatin (an organicacid with a pKa of 4.46), was transported in the secretory and absorptivedirections across Caco-2 cell monolayers. Methods. Caco-2 cells were grown on polycarbonate membrane insertsin 6-well Snapwell plates (Costar). The permeability of radiolabeledcompounds across Caco-2 cell monolayers was determined using aside-by-side diffusion apparatus (NaviCyte) and an automated liquidhandler (Hamilton Microlab 2200). The apical uptake of¹⁴C-atorvastatin was also determined in Caco-2 cells. Cyclosporin A (20 M) waspresent in the uptake media to block potential P-glycoprotein-mediatedatorvastatin efflux. Results. Polarized permeation of atorvastatin was observed with thebasolateral-to-apical (B-to-A) permeability being 7-fold greater thanthe A-to-B permeability (35.6 × 10^–6 and 4.9 × 10^–6 cm/s,respectively). The secretion of atorvastatin was a saturable process with anapparent K_m of 115 M. The B-to-A permeability of atorvastatin wassignificantly reduced by cyclosporin A (10 M), verapamil (100 M),and a P-glycoprotein specific monoclonal antibody, UIC2(10 g/ml)(43%, 25%, and 13%, respectively). Furthermore, both CsA andverapamil significantly increased the A-to-B permeability of atorvastatinby 60% however, UIC2 did not affect the A-to-B permeability ofatorvastatin. CsA uncompetitively inhibited the B-to-A flux ofatorvastatin with a K_i of 5 M. In addition, atorvastatin (100 M) significantlyinhibited the B-to-A permeability of vinblastine by 61%. The apicaluptake of atorvastatin increased 10.5-fold when the apical pH decreasedfrom pH 7.4 to pH 5.5 while the pH in the basolateral side wasfixed at pH 7.4. A proton ionophore, carbonylcyanidep-trifluoro-methoxyphenylhydrazone (FCCP) significantly decreased atorvastatinuptake. In addition, atorvastatin uptake was significantly inhibited bybenzoic acid, nicotinic acid, and acetic acid each at 20 mM (65%,14%, and 40%, respectively). Benzoic acid competitively inhibitedatorvastatin uptake with a K_i of 14 mM. Similarly, benzoic acid,nicotinic acid, and acetic acid significantly, inhibited the A-to-Bpermeability of atorvastatin by 71%, 21%, and 66%, respectively. Conclusion. This study demonstrated that atorvastatin was secretedacross the apical surface of Caco-2 cell monolayers viaP-glycoprotein-mediated efflux and transported across the apical membrane in theabsorptive direction via a H⁺-monocarboxylic acid cotransporter(MCT). In addition, this study provided the first evidence thatnegatively charged compounds, such as atorvastatin, can be a substrate forP-glycoprotein.     

阿伐他汀对成年大鼠心肌成纤维细胞分泌内皮素-1及一氧化氮合酶/一氧化氮系统活性的影响

目的 :探讨阿伐他汀 (Atorvastatin)对大鼠心肌成纤维细胞 (CFs)分泌内皮素 1(ET 1)含量及一氧化氮合酶 /一氧化氮 (NOS NO)系统活性的影响。　方法 :采用胰蛋白酶和胶原酶混合消化法 ,差速贴壁获取CFs。应用放免法、硝酸还原酶法和分光光度法分别测定不同干预条件下CFs培养液中ET 1水平及NOS NO活性。　结果 :①阿伐他汀呈浓度依赖性抑制CFs分泌ET 1,10 -6、10 -5和 10 -4mol/L阿伐他汀组与对照组相比差异非常显著 (均P <0 .0 1) ;10 -5和 10 -4mol/L阿伐他汀组分别与 10 -7和 10 -6mol/L阿伐他汀组相比差异非常显著 (均P <0 .0 1)。②阿伐他汀可升高CFsNO含量 ,10 -5和 10 -4mol/L阿伐他汀组与对照组相比差异显著 (P <0 .0 5 )和非常显著 (P <0 .0 1) ;10 -4mol/L阿伐他汀组与 10 -7mol/L阿伐他汀组相比差异显著 (P <0 .0 5 )。③阿伐他汀可增强CFsNOS活性 ,10 -5和 10 -4mol/L组阿伐他汀与对照组相比差异显著 (P <0 .0 5 )或非常显著 (P <0 .0 1) ;10 -4mol/L与 10 -7mol/L阿伐他汀组相比差异显著 (P <0 .0 5 )。　结论 :阿伐他汀能抑制CFs分泌ET 1,提高CFsNOS NO系统活性 ,拮抗血管紧张素Ⅱ (AngⅡ )的部分生物活性 ,发挥其逆转心室重塑、改善心功能的作用     

普罗布考联合阿托伐他汀对急性冠脉综合征患者妊娠相关血浆蛋白和高敏C反应蛋白的影响

目的 比较急性冠脉综合征(ACS)患者早期使用普罗布考联合阿托伐他汀与单用阿托伐他汀对妊娠相关血浆蛋白A(PAPP-A)及高敏C反应蛋白(hs-CRP)的影响.方法 将90例ACS患者随机分为单独治疗组(阿托伐他汀20mg/d)和联合治疗组(普罗布考1g/d,阿托伐他汀20mg/d).分别测量两组患者服药前和服药1个月时的血清PAPP-A、hs-CR水平.结果 单独治疗组治疗前血清PAPP-A和hs-CRP水平分别为(2.09±0.69)mIU/L和(4.17±2.93)mg/L,治疗后降至(1.68±0.40)mIU/L和(2.33±2.25)mg/L.联合治疗组治疗前血清PAPP-A和hs-CRP水平分别为(2.25±0.64)mIU/L和(5.18±4.56)mg/L,治疗后降至(1.54±0.38)mIU/L和(1.60±1.11)mg/L.两组患者治疗后血清PAPP-A和hs-CRP水平较治疗前均明显降低(P＜0.01),但联合治疗组降低的幅度较单独治组大(P＜0.05).多因素直线相关分析显示ACS患者的血清PAPP-A与hs-CRP显著相关(r=0.378,P＜0.01).结论 短期使用普罗布考联合阿托伐他汀与单用阿托伐他汀均能降低ACS患者血清PAPP-A与hs-CRP水平,可能起到抑制炎症反应、稳定冠状动脉粥样斑块的作用.加用普罗布考可能发挥进一步稳定斑块的作用.     

非诺贝特和阿托伐他汀对ApoE基因敲除小鼠外周血单核细胞TLR4表达的影响

目的 探讨非诺贝特和阿托伐他汀对动脉粥样硬化(atherosclerosis, AS)模型小鼠单核细胞Toll样受体4(Toll-like receptor 4, TLR4)表达的影响.方法 apoE基因缺陷(apoE deficient,apoE-/-)小鼠被随机分为3组,分别为阿托伐他汀干预组、非诺贝特干预组、模型组,每组10只.前两组分别给予阿托伐他汀10 mg·kg-1·d-1和非诺贝特100 mg·kg-1·d-1,对照组给予等量蒸馏水灌胃.8周后,测定血清低密度脂蛋白(LDL)、甘油三酯(TG)、总胆固醇(TC)水平,并应用流式细胞仪检测各组小鼠外周血单核细胞表面TLR4的表达.结果 各组小鼠血脂水平无统计学差异.与单纯高脂餐喂养组相比,非诺贝特干预组小鼠TLR4表达明显降低(P=0.02);阿托伐他汀干预组TLR4表达轻度升高,但无统计学意义.结论 非诺贝特可降低TLR4表达,可能参与AS进程中介导的天然免疫反应.     

阿托伐他汀对稳定型心绞痛患者外周血T细胞亚组影响的初步研究

目的探讨阿托伐他汀对稳定型心绞痛患者外周血T淋巴细胞免疫的影响。方法借助三色荧光标记技术对27例行冠状动脉支架术治疗的稳定型心绞痛患者服用阿托伐他汀前和3个月后外周血T细胞上共刺激分子CD28的表达以及CD28-抑制性T细胞的变化进行流式细胞术测定,并用ELISA法检测血浆CD40L水平。结果阿托伐他汀服用6个月后,外周血采集物中CD4 和CD8 细胞亚组以及CD28 和CD28-亚组细胞相对数无显著变化,血浆CD40L水平与服药前比较明显降低。结论阿托伐他汀虽不能使稳定型心绞痛患者外周血中T淋巴细胞亚组构成发生变化,但能降低血小板源性的T淋巴细胞激活物sCD40L。     

Atorvastatin reduces serum leptin concentration in hypercholesterolemic rabbits

BACKGROUND: Leptin may play an important role in the development of atherosclerosis. We evaluated the effect of atorvastatin on leptin secretion in vivo and in vitro. METHODS: Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) high cholesterol diet for 6 weeks (n=8), and (2) the same cholesterol diet plus atorvastatin (2.5 mg/kg/day) for 6 weeks (n=8). A control group (n=5) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of atorvastatin on leptin release was assayed in primary rabbit adipocytes. Leptin levels in serum and adipocytes culture supernatant were measured by ELISA. RT-PCR was used to evaluate leptin mRNA expressions in adipose and adipocytes. RESULTS: Compared with control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol, LDL cholesterol and leptin, all of which were significantly reduced by atorvastatin treatment. Leptin mRNA expression of adipose was significant lower in rabbits treated with atorvastatin than those fed with high cholesterol diet continuously (0.81+/-0.31 vs. 1.23+/-0.36, P<0.05). Atorvastatin dose-dependently inhibited leptin secretion and mRNA expression in cultured adipocytes. CONCLUSION: Atorvastatin can inhibit leptin release and mRNA expression, and reduces serum leptin level in hypercholesterolemic rabbits.     

阿托伐他汀在不稳定性心绞痛患者早期应用中对C反应蛋白影响的研究

目的研究不稳定性心绞痛患者接受阿托伐他汀治疗3d后对血浆高敏-C反应蛋白(hs-CRP)及血脂水平的影响。方法选择2003年5月～2004年5月住院94例不稳定性心绞痛患者为研究对象,随机分为两组,常规治疗组47例,给予抗凝、硝酸酯类、β受体阻滞剂、血管紧张素转换酶抑制剂和钙拮抗剂等药物;阿托伐他汀干预组47例,在常规治疗基础上加用阿托伐他汀(商品名:阿乐)每日20mg,治疗3d,并测定两组治疗前后hs-CRP及血脂水平变化。结果治疗3d后,阿托伐他汀干预组血浆hs-CRP水平较常规治疗组明显降低(P<0.01),但两组治疗前后各血脂成分的变化差异无显著性。结论不稳定心绞痛患者较大剂量阿托伐他汀治疗3d后,可明显降低血浆hs-CRP水平,从而抑制冠心病患者炎性反应,有利于动脉粥样硬化斑块的稳定性,且该作用并不依赖于血脂的变化。