辛伐他汀对新诊断糖耐量减低个体血脂、胰岛素抵抗及炎症因子影响

目的:比较辛伐他汀标准和强化治疗对新诊断糖耐量减低(IGT)病人血脂谱、胰岛素抵抗(IR)及血清炎症因子的影响。方法:106例伴有不同程度血脂异常的新诊断IGT病人随机分为2组:常规组54例,男性26例,女性28例,年龄(54±s6)a;强化组52例,男性27例,女性25例,年龄(52±6)a。在给予生活方式干预的同时常规组予辛伐他汀20mg·d~(-1),强化组予辛伐他汀40mg·d~(-1),均睡前服药,疗程为12 wk。比较治疗前后血脂、胰岛素抵抗指数(IRI)、及血清高敏C反应蛋白(HS—CRP)、纤维蛋白原(FIB)的变化。结果:2组治疗后三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、HS-CRP均明显降低(P<0.01),强化组的下降幅度大于常规组,差异非常显著(P<0.01)。强化组IRI和空腹胰岛素(FINS)治疗后亦降低(P<0.01),而常规组无显著变化(P>0.05),2组间有非常显著差异(P<0.01)。强化组不良反应发生率8%,常规组6%(P>0.05)。结论:对IGT合并血脂异常病人予他汀类药物治疗能有效改善血脂谱、减轻IR和炎症状态,并有良好的安全性。     

Simvastatin induces osteogenic differentiation of murine embryonic stem cells

Statins are potent inhibitors of cholesterol synthesis. Several statins are available with different molecular and pharmacokinetic properties. Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin, allowing its passive diffusion through the cell membrane. In vitro studies on bone marrow stromal cells, osteoblast‐like cells, and embryonic stem cells have shown statins to have cholesterol‐independent anabolic effects on bone metabolism; alas, statins were supplemented in osteogenic medium, which does not facilitate elucidation of their potential osteoinductive properties. Embryonic stem cells (ESCs), derived from the inner cell mass of the blastocyst, are unique in that they enjoy perpetual self‐proliferation, are pluripotent, and are able to differentiate toward all the cellular lineages composing the body, including the osteogenic lineage. Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases, even though there are several hurdles that still need to be overcome. Herein we demonstrate, for the first time to our knowledge, that simvastatin induces murine ESC (mESC) differentiation toward the osteogenic lineage in the absence of osteoinductive supplements. Specifically, we found that a simvastatin concentration in the micromolar range and higher was toxic to the cells and that an effective concentration for osteoinduction is 0.1 nM, as shown by increased alizarin red staining as well as increased osteocalcin and osetrix gene expression. These results suggest that in the future, lipophilic simvastatin may provide a novel pharmacologic agent for bone tissue engineering applications. © 2010 American Society for Bone and Mineral Research.     

Efficacy and safety of simvastatin (alone or in association with cholestyramine). A 1-year study in 66 patients with type II hyperlipoproteinaemia

The effects and safety of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, were investigated alone or in association with cholestyramine in 66 patients with hypercholesterolaemia, in a 1-year study. In type IIa hypercholesterolaemia (41 patients), the association was more effective than simvastatin used alone in lowering total cholesterol (37% vs 29%) and LDL-cholesterol (45% vs 37%). In type IIb hypercholesterolaemia (23 patients), the association simvastatin-cholestyramine did not appear more effective than simvastatin used alone. The decrease of apoprotein B was parallel to the LDL-cholesterol decrease. Apoprotein A1 did not change significantly. The long-term safety of simvastatin was good. No lens opacity was noted. The most serious side-effect in our study was myolysis which occurred in two patients with a marked increase in creatine phosphokinase.     

Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans

BACKGROUND: As statin therapy has been reported to reduce antioxidants such as vitamin E and coenzyme Q10 and there are indications that this reduction may cause impairment of left ventricular function (LVF), we studied the influence of simvastatin on LVF and serum vitamin E and coenzyme Q10 levels in humans. MATERIAL AND METHODS: We assessed the effect of simvastatin on left ventricular function and coenzyme Q10 levels in 21 (11 male, 10 female) hypercholesterolaemic subjects (mean age = 56 years) with normal LVF, over a period of 6 months. Subjects were re-tested after a 1-month wash-out period (7 months). Echocardiography was performed on all subjects before commencement of simvastatin (20 mg day(-1)), and at 1, 3, 6 and 7 months after initiation of treatment. Fasting blood samples were also collected at these intervals to assess lipids, apoproteins, vitamin E and coenzyme Q10. RESULTS: Serum lipids showed the expected reductions. Plasma vitamin E and coenzyme Q10 levels were reduced by 17 +/- 4% (P < 0.01) and 12 +/- 4% (P < 0.03) at 6 months. However, the coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio increased significantly. Left ventricular ejection fraction (EF) decreased transiently after 1 month, while no significant change was observed at 3 and 6 months. Other markers of left ventricular function did not change significantly at any time point. CONCLUSION: Despite reduced plasma vitamin E and coenzyme Q10, 20 mg of simvastatin therapy is associated with a significantly increased coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio. Simvastatin treatment is not associated with impairment in left ventricular systolic or diastolic function in hypercholesterolaemic subjects after 6 months of treatment.     

Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation

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An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia

Abstract

Background:

Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III.

Objective:

The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia.

Methods:

This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting.

Results:

Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin.

Conclusions:

In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.Key words: dyslipidemia, simvastatin, niacin, combination therapy     

辛伐他汀对不稳定型心绞痛患者血清sCD40L水平的影响

目的：探讨辛伐他汀对不稳定型心绞痛患者血清中可溶性CD40L（sCD40L）水平的影响。方法：48例ACS患者随机分为2组：A组（安慰剂组）,B组（辛伐他汀组）。采用间接免疫荧光流式细胞术和酶联免疫吸附法（ELISA）及常规酶法分别测定2组患者用药前与用药2、4和6周后血清sCD40L含量及总胆固醇（TC）水平。结果：B组患者服药2、4及6周后血清sCD40L含量明显低于A组（P〈0.05,P〈0.01,P〈0.01）。B组患者服药2、4及6周后血清sCD40L含量呈逐渐下降趋势,同用药前相比均有显著性差异（P〈0.05,P〈0.01,P〈0.01）。B组患者服药2、4及6周后血浆TC含量与用药前相比均有统计学意义（P〈0.05,P〈0.01,P〈0.01）。B组患者血清sCD40L水平的降低与血浆TC含量的降低无明显相关性（P〉0.05）。结论：他汀类药物能明显降低不稳定型心绞痛患者体内sCD40L的水平,对减轻炎症反应、稳定斑块有一定作用。     

辛伐他汀对糖尿病血脂异常的调节作用

目的　了解辛伐他汀对糖尿病血脂异常的调节作用。方法　比较 6 3例 2型糖尿病合并血脂异常采用胰岛素强化治疗 [即胰岛素泵持续皮下注射胰岛素 (CSII)或者多次 (>4次 /d)皮下注射胰岛素 (MSII) ]并连续服用辛伐他汀 2周与 4 2例 2型糖尿病合并血脂异常单纯采用胰岛素强化治疗 (CSII或者MSII) 2周后血脂的变化情况 ,同时了解治疗前后的空腹血糖 (FBS)、餐后 2小时血糖、肝功能 (LF)、肾功能 (SPS)及心肌酶学等的变化。结果　胰岛素强化治疗并连续服用辛伐他汀治疗组血脂显著变化 (P <0 .0 0 1 ) ,而单纯胰岛素强化治疗组血脂变化不明显 (P >0 .0 5 ) ,前者调节糖尿病合并血脂异常有效率达 93.6 % ,且副作用发生率低 (7.93% )而轻微。结论　辛伐他汀对 2型糖尿病合并血脂异常的调节作用疗效肯定 ,副反应小 ,可作为常用药物     

大鼠急性心肌梗死后心脏炎症细胞因子基因和蛋白表达及辛伐他汀干预研究

目的探讨辛伐他汀对急性心肌梗死(AMI)后大鼠心脏炎症细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)mRNA表达和蛋白质产生的影响。方法Wistar大鼠36只分3组:(1)假手术(Sham)组;(2)心肌梗死对照(MI-C)组;(3)辛伐他汀(MI-S)组。动物笼养4周取出心脏,沿乳头肌等分为二,一半用逆转录聚合酶链反应法测定心脏细胞因子mRNA表达,另一半用Western blot测定细胞因子蛋白质生成量。结果Sham组上述细胞因子均无明显表达,MI-C组TNF-α,IL-1β,IL-6和IL-10 mRNA和蛋白产生均显著高于Sham组;同MI-C组比较,MI-S组的TNF-α,IL-1β,IL-6 mRNA和蛋白生成均显著下降,而IL-10的mRNA和蛋白明显升高。结论辛伐他汀明显降低AMI后大鼠心脏的致炎症细胞因子,而升高炎症保护因子IL-10。