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Exploration of a combination Phytosterol and Ezetimibe therapy for the treatment of combined dyslipidemia in a Syrian golden hamster model.

机译:探索植物甾醇和依泽替米贝的组合疗法在叙利亚金仓鼠模型中治疗合并的血脂异常。

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摘要

Ezetimibe (EZ) and Phytosterols (PS) are the best-defined drug and nutraceutical approaches for lowering blood cholesterol. Furthermore, both EZ and PS appear to have triglyceride (TAG)-lowering properties through as of yet unknown effects on intestinal lipid metabolism. Our work sought to examine blood lipid responses and changes in the expression of intestinal lipid-related proteins from treatment with EZ, PS, or a PS/EZ combination in Syrian golden hamsters. Forty-eight (n=12) male hamsters were assigned to 4 groups for 6 weeks: (a) Atherogenic diet (ATH); (b) ATH + 2% PS; (c) ATH + 0.002% EZ; and (d) ATH + PS/EZ. Compared with the ATH diet, non-HDL-C and TAG were reduced (p<0.05) in response to PS (88 and 64%), EZ (100 and 103%), and PS/EZ (99 and 101%), with no difference ( P>0.05) between the single vs. combined therapies. Cholesterol absorption was reduced (p<0.05) in the PS (27%), EZ (37%), and PS/EZ (38%) groups compared with the ATH group. Intestinal NPC1L1 protein abundance was reduced in the EZ group (1.44, p<0.05) while SREBP1c mRNA expression was reduced in the PS and PS/EZ groups (2.19 fold and 2.02 fold respectively, p<0.05). These results suggest that PS and EZ are effective treatments for combined dyslipidemia but no additional benefits are gained from a combined therapy. Additionally, our results reveal the possible mechanism whereby EZ and PS differentially modify intestinal CHOL absorption and serum TAG. We conclude that EZ exerts its effects through reductions in NPC1L1 while PS acts by reducing SREBP1c mRNA expression.
机译:依泽替米贝(EZ)和植物甾醇(PS)是降低血液胆固醇的最佳药物和营养保健品。此外,EZ和PS似乎都具有降低甘油三酸酯(TAG)的特性,原因是对肠道脂质代谢的影响尚未知。我们的工作试图通过叙利亚金仓鼠中的EZ,PS或PS / EZ组合治疗来检查血脂反应和肠道脂质相关蛋白表达的变化。将四十八只(n = 12)雄性仓鼠分为4组,共6周:(a)致动脉粥样硬化饮食(ATH); (b)ATH + 2%PS; (c)ATH + 0.002%EZ; (d)ATH + PS / EZ。与ATH饮食相比,对PS(88%和64%),EZ(100%和103%)和PS / EZ(99%和101%)的反应,非HDL-C和TAG降低(p <0.05),单一疗法与联合疗法之间无差异(P> 0.05)。与ATH组相比,PS(27%),EZ(37%)和PS / EZ(38%)组的胆固醇吸收降低(p <0.05)。 EZ组的肠道NPC1L1蛋白丰度降低(1.44,p <0.05),而PS和PS / EZ组的SREBP1c mRNA表达降低(分别为2.19倍和2.02倍,p <0.05)。这些结果表明,PS和EZ是治疗合并血脂异常的有效方法,但联合治疗未获得其他益处。此外,我们的结果揭示了EZ和PS差异修饰肠道CHOL吸收和血清TAG的可能机制。我们得出的结论是,EZ通过减少NPC1L1发挥作用,而PS通过减少SREBP1c mRNA表达发挥作用。

著录项

  • 作者

    Griffin, John D.;

  • 作者单位

    State University of New York at Buffalo.;

  • 授予单位 State University of New York at Buffalo.;
  • 学科 Health Sciences Nutrition.
  • 学位 M.S.
  • 年度 2012
  • 页码 68 p.
  • 总页数 68
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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