Reduction of oxidative stress and modulation of autoantibodies against modified low-density lipoprotein after rosuvastatin therapy

AIMS: To examine the effect of 24 weeks' rosuvastatin treatment on oxidative stress and changes in immune response to oxidized low-density lipoprotein (LDL). METHODS: This was an open-label study of patients in Austria receiving 10 or 40 mg rosuvastatin daily alternately during 12 and 24 weeks. Circulating concentrations of antibodies to malondialdehyde-oxidized LDL (MDA-LDL), both IgG and IgM type, to copper-oxidized LDL (Cu-OxLDL-IgG), concentrations of oxidized LDL complexed to IgG (OxLDL-IC) and markers of oxidative stress and systemic inflammation in subjects with plasma LDL cholesterol concentrations between 130 mg dl-1 and 250 mg dl-1 and triglyceridesrosuvastatin significantly reduces oxidative stress and has immunomodulatory properties in a dose- and LDL-independent manner.     

瑞舒伐他汀通过调控UCP2-SIRT3通路减轻脑缺血/再灌注对神经元线粒体的损伤

目的探讨瑞舒伐他汀(rosuvastatin,RS)通过UCP2-SIRT3信号通路在脑缺血/再灌注(CIR)神经元线粒体损伤中的作用及其机制。方法建立SH-SY5Y细胞的脑梗死再灌注模型(OGD/R),给予不同浓度RS(40和2.5μmol·L^-1)分别处理,观察两组中细胞增殖和凋亡的变化及UCP2和SIRT3分子的表达;构建UCP2沉默细胞系,研究不同浓度RS对UCP2沉默前后细胞形态和线粒体膜电位的影响、以及SIRT3分子、线粒体外膜异位酶20(TOMM20)和线粒体合成相关蛋白(Drp1、Opa1和PGC1)的表达变化。结果RS能提高OGD/R细胞的存活率、抑制细胞凋亡、改变细胞形态、稳定细胞线粒体膜电位;增加OGD/R细胞中UCP2、SIRT3分子和TOMM20蛋白表达,并诱导Drp1和Opa1 mRNA的表达,抑制PGC1 mRNA的表达;沉默UCP2后能明显降低OGD/R细胞的存活率及TOMM20蛋白的表达,降低Drp1和Opa1 mRNA的表达,使PGC1 mRNA的表达增加。结论RS通过调控UCP2-SIRT3通路减轻CIR对神经元线粒体的损伤,发挥神经细胞保护作用。     

液相色谱-串联质谱法测定人血浆中瑞舒伐他汀钙浓度及临床药代动力学研究

目的：建立测定人血浆中瑞舒伐他汀钙的液相色谱．串联质谱法，考察瑞舒伐他汀钙在中国健康志愿者体内的药代动力学。方法：含有瑞舒伐他汀钙和氟伐他汀钠的血浆样品经液-液提取后，进行色谱分析，在三重四极杆串联质谱仪上，以多反应离子监测方式进行定量分析。结果：瑞舒伐他汀钙的定量下限为0．03ng／mL，线形范围为0．03～60ng／mL，精密度与准确度符合生物样品分析要求。结论：该方法操作简便、快速、灵敏度高，适合瑞舒伐他汀钙的临床药代动力学研究。     

(3R,5S)-6-氧代-3,5-O-亚异丙基-3,5-二羟基己酸叔丁酯的合成

L-（-）-苹果酸经酯化、还原、羟基保护、缩合、羰基还原、羟基保护、脱硅保护和Swern氧化等反应制得罗伐他汀的关键中间体（3R，5S）-6-氧代-3,5-O-亚异丙基-3，5-二羟基己酸叔丁酯，总收率25％。     

Effects of Rosuvastatin on Asymmetric Dimethylarginine Levels and Early Atrial Fibrillation Recurrence after Electrical Cardioversion

Background: High levels of asymmetric dimethylarginine (ADMA) are associated with an increased risk of early recurrence of atrial fibrillation (AF) after electrical cardioversion. We aimed to investigate the effects of rosuvastatin on serum ADMA levels and early recurrence of AF following successful electrical cardioversion. Methods: A total of 64 patients with persistent AF, but without known heart disease, who underwent elective electrical cardioversion were randomized to the rosuvastatin (group I, n = 32) and control (group II, n = 32) groups. The end point was the recurrence of AF during the 3 months of follow‐up. Results: The baseline ADMA levels were not different between the two groups. At the end of follow‐up, serum ADMA levels in group I decreased compared with the baseline levels, whereas no significant change occurred in group II. During the follow‐up, five patients in group I (15.6%) and 13 in group II (40.6%) had AF recurrence (P < 0.05, log‐rank test). With the Cox proportional model, the predictors of recurrence included age ≥65 years, left atrial diameter >45 mm, and baseline ADMA levels ≥2.0 μmol/l. Rosuvastatin was associated with a reduced risk of AF recurrence (relative risk 0.35, 95% confidence interval 0.12–0.96, P < 0.05). Conclusions: Rosuvastatin decreased the early recurrence of AF following successful electrical cardioversion with reduced ADMA levels.     

血脂康联合非诺贝特治疗2型糖尿病合并高血脂症的临床疗效及安全性评价

【】 目的 评价血脂康联合非诺贝特治疗2型糖尿病合并高血脂症的临床疗效及安全性。 方法 将80例高脂血症患者随机分为两组,其中对照组40例,每晚给予瑞舒伐他汀钙片10mg口服, qd；治疗组40例,给予血脂康0.6g,bid,早晚饭后服用,在此基础上给予非诺贝特胶囊(II)200 mg,qd,每天早晨与餐同服,疗程8周。观察两组患者在治疗前后血脂和血糖等指标的变化情况。 结果 治疗8周后,两组患者的血脂水平与治疗前相比均有明显改善,其中TC、TG和LDL-C较治疗前显著降低,而HDL-C较治疗前明显升高(P < 0.01)；治疗组在TC和TG的降幅上要优于对照组,而对照组在LDL-C的降幅上大于治疗组,差异有统计学意义(P < 0.05)。在血糖控制方面,治疗组能降低患者FPG和2hPG的水平(P < 0.05),尤其是显著降低患者的HbA1c水平(P < 0.01)；而对照组患者的治疗前后血糖基本没有影响(P > 0.05)。 结论 血脂康联合非诺贝特治疗2型糖尿病合并高血脂症能显著改善患者的血脂和血糖水平,同时安全性好,值得临床推广。     

Novel statins: pharmacological and clinical results

Rosuvastatin (ZD4522) and pitavastatin (NK-104) are novel HMG-CoA reductase inhibitors with a peculiar pharmacological profile. In particular, they show a high potency in decreasing LDL-C and their catabolism is not mediated by the cytochrome P-450 3A4, thus reducing the potential for drug-drug interaction and improving the management of blood cholesterol. As the magnitude of LDL-C reduction is directly associated with the decrease in the incidence of myocardial infarction and mortality for CAD, statins with increased LDL-C lowering potency may ensure the achievement of target LDL-C levels and offer a more aggressive cholesterol control, further improving CAD morbidity and mortality.     

钠-葡萄糖协同转运蛋白2抑制剂对肿瘤影响的研究进展

目的 对比分析阿托伐他汀和瑞舒伐他汀所致药品不良反应,为临床安全、合理选择降脂药提供参考。方法 采用回顾性分析的方法,对福州市长乐区医院2010—2019年上报的怀疑阿托伐他汀和瑞舒伐他汀所致不良反应病例报告进行对比分析。分别从患者一般情况、用药情况、累及系统-器官损害、观察指标、不良反应发生时间分布、及转归等方面进行统计分析。结果 共筛选出89例阿托伐他汀所致的不良反应报告、38例瑞舒伐他汀所致的不良反应报告。阿托伐他汀以肝胆系统损害及骨骼肌系统损害多见,瑞舒伐他汀以肝胆系统及泌尿系统损害多见;阿托伐他汀涉及系统器官的不良反应表现较多,阿托伐他汀和瑞舒伐他汀出现的LFTs>3×ULN、CK>10×ULN、SAMS的比较差异均无统计学意义。阿托伐他汀不良反应多发生在用药4～18 d,而瑞舒伐他汀多发生在5～20 d。阿托伐他汀与瑞舒伐他汀引起的不良反应大部分为严重,经采取相应措施治疗后易于好转及治愈。结论 阿托伐他汀与瑞舒伐他汀引发的不良反应临床表现有所不同,但不良反应发生时间及主要不良反应观察指标相似,临床用药中应当根据实际情况进行使用,以保障用药安全。