Development of Atherosclerosis on Tsukuba Hypertensive Mice

筑波高血压小鼠动脉粥样硬化的发展

• 批准号: 07680909
• 负责人: SUGIYAMA Fumihiro
• 金额: $ 1.41万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680909/
• 关键词: Atherosclerosis; Hypertension; Renin-Angiotensin System; Transgenic mice

The present study was designed to investigate the development of atherosclerotic lesions in hypertensive transgenic mice carrying both the human renin and human angiotensinogen genes (Tsukuba hypertensive mice ; THM). THM and C57BL/6J control mice at those ages of 2-3 months were fed with either an atherogenic or a normal diet for 14 weeks. Although systolic blood pressure of THM was significantly higher than that of C57BL/6J on both diets, it did not change on the atherogenic diet in each strain. Total plasma cholesterol concentrations in mice on the atherogenic diet were significantly higher levels than those in mice fed with the normal diet. Lipoprotein profiles of cholesterol in THM were fundamentally similar to those in C57BL/6J either on the atherogenic or normal diet. Compared with controls, however, microscopic analyzes revealed the accelerated damage of cellular structure on aortic root in THM fed with the atherogenic diet. Remarkably, the surface area of atherosclerotic lesion in THM was shown to be four times larger than that in C57BL/6J on the same atherogenic diet by a quantitative image analysis. These findings suggested that hypertension induced by the activated renin-angiotensin system is definitely involved in the development of atherosclerotic lesions. THM should be a useful model animal for the study on the pathogenesis of atherosclerosis.

本研究的目的是调查的发展动脉粥样硬化病变的高血压转基因小鼠携带的人肾素和人血管紧张素原基因（筑波高血压小鼠; THM）。给2-3个月龄的THM和C57 BL/6 J对照小鼠喂食致动脉粥样硬化饮食或正常饮食14周。虽然在两种饮食中，THM的收缩压显著高于C57 BL/6 J，但在每种品系中，THM的收缩压在致动脉粥样硬化饮食中没有变化。食用致动脉粥样硬化饮食的小鼠血浆总胆固醇浓度显著高于食用正常饮食的小鼠。THM中胆固醇的脂蛋白谱与C57 BL/6 J中的脂蛋白谱基本相似，无论是在致动脉粥样硬化还是正常饮食中。然而，与对照组相比，显微镜分析显示，动脉粥样硬化饮食喂养的THM主动脉根部细胞结构加速损伤。值得注意的是，通过定量图像分析显示，THM中动脉粥样硬化病变的表面积是相同致动脉粥样硬化饮食的C57 BL/6 J中的4倍。这些结果表明，由激活的肾素-血管紧张素系统诱导的高血压肯定参与了动脉粥样硬化病变的发展。THM是研究动脉粥样硬化发病机制的理想模型动物。

项目成果

Watanabe Y., Ebukuro M., Yagami K., Sugiyama F., Ishida J.Murakami K., Nomura T., and Katoh H.: "Chromosomal mapping of human angiotensinogen gene and human renin gene by fluorescence in situ hybridization (FISH) in transgenic mice.Exp." Anim. 45. 265-269

Watanabe Y.、Ebukuro M.、Yagami K.、Sugiyama F.、Ishida J.Murakami K.、Nomura T. 和 Katoh H.：“通过荧光原位杂交（FISH）对人血管紧张素原基因和人肾素基因进行染色体定位

杉山 文博: "高血圧とそれに伴う臓器障害の発症機構" BIO Clinica. 11・7. 522-525 (1996)

Fumihiro Sugiyama：“高血压和相关器官损伤的发病机制”BIO Clinica 11・7（1996）。

杉山文博ら: "つくば高血圧マウスと妊娠高血圧マウス" KIDS. 7 印刷中. (1997)

Fumihiro Sugiyama 等人：“筑波高血压小鼠和妊娠高血压小鼠”KIDS 7（1997 年）。

Takimoto E., Ishida J., Sugiyama F., Horiguchi H., Murakami K., and Fukamizu A.: "Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen" Science. 274. 995-998 (1996)

Takimoto E.、Ishida J.、Sugiyama F.、Horiguchi H.、Murakami K. 和 Fukamizu A.：“胎盘肾素和母体血管紧张素原诱导妊娠小鼠高血压”《科学》。

Sugiyama F., Fukamizu A., Miyazaki H., Yagami K., and Murakami K.: "Developmental mechanism in organ disorder combined with hypertension (Japanese)" BIO Clinica. 11. 522-525 (1996)

Sugiyama F.、Fukamizu A.、Miyazaki H.、Yagami K. 和 Murakami K.：“器官疾病合并高血压的发育机制（日语）”BIO Clinica。