PPARα转基因小鼠在药物临床前评价中的应用研究

发布时间：2018-03-08 14:47

本文选题：PPARα　切入点：转基因小鼠　出处：《北京协和医学院》2013年硕士论文　论文类型：学位论文

【摘要】：过氧化物酶体增殖激活受体(peroxisome proliferators-activated receptor,PPAR)是核受体家族的一部分。有三个不同的PPAR,包括α,β,γ。PPARα是脂肪酸氧化酶基因的主要转录调控子,PPARα激动剂临床上主要应用于高甘油三酯血症的治疗中。人类疾病的转基因动物模型具有与人类相似疾病在致病原因、机制相同的优点,已被越来越多的科研人员用于药物评价中。本研究利用PPARα转基因小鼠,通过对PPARα激动剂药物的药效学、毒理学评价,本实验从三个方面展开： 1.PPARα转基因对小鼠的生理、生化等影响的研究本试验旨在针对不同周龄的PPARα转基因小鼠,测定其体重、生理、生化、组织病理学指标,收集不同周龄的PPARα转基因小鼠的体重、生理、生化、组织病理学指标的数据,为新药临床前评价工作深入研究提供科学的基础数据。通过分析PPARα转基因小鼠的相关数据,我们初步探究了PPARα转基因对小鼠的生理、生化指标的影响。 2.PPARα转基因小鼠在药物药效学评价中的应用研究本试验使用PPARα转基因小鼠进行PPARα激动剂药物的药效学评价,初步探究了在评价PPARα激动剂药效学方面PPARα转基因小鼠是一种药效学敏感的动物模型；能用于该类药物的早期筛选,为药物研发机构节约时间和经费。 3.PPARα转基因小鼠在药物毒理学评价中的应用研究本试验使用PPARα转基因小鼠进行PPARα激动剂药物的毒理学评价。通过与野生型C57BL/6小鼠比较,初步进行了PPARα转基因小鼠在评价PPARα激动剂毒理学的试验研究。
[Abstract]:Peroxisome proliferators-activated receptor (PPAR) is part of the nuclear receptor family. There are three different PPARs, including 伪, 尾, 纬. PPAR 伪, which are the major transcriptional regulators of fatty acid oxidase genes. The genetically modified animal model of human disease has a disease similar to that of the human being in the cause of the disease. The same mechanism has been used in drug evaluation by more and more researchers. In this study, the pharmacodynamics and toxicology of PPAR 伪 agonist drugs were evaluated from three aspects:. 1. Effects of PPAR 伪 gene on physiology and biochemistry in mice. The purpose of this study was to measure the body weight, physiological, biochemical and histopathological indexes of PPAR 伪 transgenic mice at different weeks of age, and to collect the data of body weight, physiology, biochemistry and histopathology of PPAR 伪 transgenic mice at different weeks of age. By analyzing the related data of PPAR 伪 transgenic mice, we preliminarily explored the effect of PPAR 伪 gene on physiological and biochemical indexes of mice. 2. Application of PPAR 伪 transgenic mice in pharmacodynamics evaluation. In this study, PPAR 伪 transgenic mice were used to evaluate the pharmacodynamics of PPAR 伪 agonist drugs. It was preliminarily explored that PPAR 伪 transgenic mice were a sensitive animal model for evaluating the pharmacodynamics of PPAR 伪 agonists and could be used in the early screening of PPAR 伪 agonists. Save time and money for drug R & D institutions. 3. Application of PPAR 伪 transgenic mice in evaluation of drug toxicology. In this study, PPAR 伪 transgenic mice were used to evaluate the toxicology of PPAR 伪 agonist drugs. Compared with wild-type C57BL / 6 mice, PPAR 伪 transgenic mice were used to evaluate the toxicology of PPAR 伪 agonists.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R-332

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