The analysis of the function of PPARγin endothelium on the attenuation of the diabetic vascular disease using PPARγendothelium specific deficient mice.

使用 PPARγ 内皮特异性缺陷小鼠分析 PPARγ 在内皮细胞中对减轻糖尿病血管疾病的功能。

基本信息

批准号：
21591142
负责人：
ADACHI Masahiro
金额：
$ 2.91万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

The synthetic PPARγligands have provided the evidence with the improvement of insulin resistance associated with adipocyte differentiation. The effective role of synthetic PPARγligands on vascular system has been reported, but the mechanism has not been clear. To study the role of PPARγexpressed in endothelial cell on the process of diabetic vascular disease, the endothelial cell specific PPARγknock out(PPARγ. E-null) mice were produced. PPARγ. E-null mice fed with high fat diet had significantly elevated systolic blood pressure compared with control PPARγ. E-wild mice. After high fat diet treatment the expression levels of Egr-1, IL-1βand IL-6 in the aorta of PPARγ. E-null mice were elevated compared with PPARγ. E-wild mice. PPARγ. E-null mice fed high fat diet showed the improvement of elevated glucose level and fewer fat accumulation in liver whereas PPARγ. E-null mice showed higher concentration of serum triglyceride and free fatty lipid levels compared with PPARγ. E-wild mice. PPARγ. E-null crossed with apoe knock out mice fed with high fat diet showed accelerated atherogenesis, but there was no significant difference in the rate of atherosclerotic region in aorta between PPARγ. E-null-apoe KO and PPARγ. wild-apoe KO mice. In this study it is proved that PPARγexpressed in endothelial cell regulates inflammation and lipid metabolism whereas PPARγexpressed in endothelial cell has no significant effect on the progression of atherogenesis in apoe knock out mice.

合成PPARγ配体为改善脂肪细胞分化相关的胰岛素抵抗提供了证据。合成PPARγ配体对血管系统的有效作用已有报道，但其机制尚未明确。糖尿病血管疾病的过程中，制备了内皮细胞特异性PPARγ敲除(PPARγ.E-null)小鼠，并用PPARγ喂养。与对照E-野生小鼠相比，高脂肪饮食的E-null小鼠的主动脉中Egr-1、IL-1β和IL-6的表达水平显着升高。与E-野生小鼠相比，高脂肪饮食的PPARγ小鼠表现出血糖水平升高和肝脏脂肪积累减少，而PPARγ小鼠则表现出更高的血清浓度。甘油三酯和游离脂肪脂质水平与E-野生小鼠相比，与高脂肪饮食喂养的Apoe基因敲除小鼠杂交，显示出动脉粥样化加速，但主动脉粥样硬化区域的发生率没有显着差异。 PPARγ。E-null-apoe KO 和 PPARγ 野生 apoe KO 小鼠。本研究证明内皮细胞中表达的 PPARγ 具有调节炎症和脂质的作用。代谢，而内皮细胞表达的 PPARγ 对 apoe 敲除小鼠的动脉粥样硬化进展没有显着影响。