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。     

阿托伐他汀在心肌细胞肥大治疗中的作用

大量研究表明阿托伐他汀可干预心室重塑的形成和发展.应用阿托伐他汀能从不同途径发挥独特的心血管保护效应.本文从心肌细胞肥大这个角度阐述阿托伐他汀对心室重塑的影响.     

阿托伐他汀治疗合并脂肪肝的高脂血症疗效观察及护理

目的评价阿托伐他汀治疗合并脂肪肝的高脂血症的疗效,观察病人的护理效果。方法25例病人口服阿托伐他汀,20mg/d,共观察12周,按血脂指标和肝脾CT表现的改善程度确定疗效。对所有病人进行问卷调查,内容包括对药物的认识、副作用的了解和护理工作满意度。结果血清胆固醇(TC)降低34%,甘油三脂(TG)降低32%,低密度脂蛋白胆固醇(LDL-C)降低30%,高密度脂蛋白胆固醇(HDL-C)升高29%。与治疗前相比均有显著性差异(P<0.01)。脂肪肝的影像学表现也有一定程度的改善[肝/脾比值(0.72±0.23)改善为(0.95±0.15),P<0.01]。病人对常用降脂药物有一定的了解,对其主要副作用也会注意观察;病人对护理工作的满意度比较高。结论阿托伐他汀是治疗合并脂肪肝的高脂血症的有效药物。在对患有高脂血症和脂肪肝的病人进行临床护理和应用他汀类药物治疗时,要特别注意采血送检的技术要求,要了解不同药物的药理和他汀类药物的注意事项,要注意对病人进行饮食、运动、药物应用知识等方面的健康教育。     

Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia

Patients with homozygous familial hypercholesterolaemia (HoFH) have markedly elevated low density lipoprotein (LDL) cholesterol levels that are refractory to standard doses of lipid-lowering drug therapy. In the present study we evaluated the effect of atorvastatin on steady state concentrations of plasma lipids and mevalonic acid (MVA), as well as on 24-h urinary excretion of MVA in patients with well characterized HoFH. Thirty-five HoFH patients (18 males; 17 females) received 40 mg and then 80 mg atorvastatin/day. The dose of atorvastatin was increased further to 120 mg/day in 20 subjects and to 160 mg/day in 13 subjects who had not achieved LDL cholesterol goal, or in whom the dose of atorvastatin had not exceeded 2.5 mg/kg body wt per day. LDL cholesterol levels were reduced by 17% at the 40 mg/day and by 28% at the 80 mg/day dosage (P<0.01). Reduction in LDL cholesterol in the five receptor negative patients was similar to that achieved in the 30 patients with residual LDL receptor activity. Plasma MVA and 24-h urinary excretion of MVA, as markers of in vivo cholesterol synthesis, were elevated at baseline and decreased markedly with treatment. Urinary MVA excretion decreased by 57% at the 40 mg/day dose and by 63% at the 80 mg/day dosage (P<0.01). There was a correlation between reduction in LDL cholesterol and reduction in urinary MVA excretion; those patients with the highest basal levels of MVA excretion and thus the highest rates of cholesterol synthesis having the greatest reduction in LDL cholesterol (r=0.38; P=0.02). Increasing the dose of atorvastatin to 120 and 160 mg/day did not result in any further reduction in LDL cholesterol or urinary MVA excretion suggesting a plateau effect with no further inhibition of cholesterol synthesis at doses of atorvastatin greater than 80 mg/day.     

阿托伐他汀对高血压大鼠动脉血压和血管平滑肌细胞离子泵活性的影响

目的探讨阿托伐他汀对自发性高血压大鼠的动脉血压及血管平滑肌细胞离子泵活性的影响。方法选用12周龄自发性高血压大鼠12只,随机分为阿托伐他汀治疗组(简称阿托伐他汀组,n=6)和蒸馏水组(n=6),并以正常血压大鼠作为对照组。阿托伐他汀组大鼠给以阿托伐他汀[50mg(kg·d)]加适量蒸馏水灌胃12周。观察给药前后大鼠尾动脉血压的变化,测定大鼠血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇浓度,以及胸主动脉平滑肌细胞Na K ATP酶和Ca2 Mg2 ATP酶活性。结果阿托伐他汀组动脉血压显著低于蒸馏水组(161.8±9.9比192.9±10.4,P<0.05);阿托伐他汀组大鼠胸主动脉平滑肌细胞Na K ATP酶和Ca2 Mg2 ATP酶活性明显高于蒸馏水组(5.20±0.54比3.06±0.42,P<0.01;4.62±0.35比2.98±0.17,P<0.05),略低于对照组,而蒸馏水组则显著低于对照组(3.06±0.42比5.92±0.31,P<0.01;2.98±0.17比4.86±0.26,P<0.01)。Na K ATP酶活性、Ca2 Mg2 ATP酶活性与血压呈显著负相关(r=-0.426、r=-0.359,P<0.01)。结论长期应用阿托伐他汀可以显著降低自发性高血压大鼠血压。阿托伐他汀可能通过增高血管平滑肌细胞离子泵活性而影响血压形成的过程。