权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Therapy for Advanced Atherosclerosis by Using Vascular Endocrinological System

血管内分泌系统治疗晚期动脉粥样硬化

基本信息

批准号：
11670672
负责人：
HAYASHI Toshio
金额：
$ 2.3万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

We tried to use vascular endocrinological system (citrulline-arginine cycle) for therapy of advanced atherosclerosis. We also tried to investigate the role of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase in aged advanced atherosclerotic animal model. Firstly, we observed iNOS and ONOO^- in T cell and macrophages in rabbit advanced atherosclerosis. Application of L-arginine but not citrulline retards progression of atherosclerosis. Secondly, we determined dothelial and non-endothelial vascular responses, eNOS and soluble guanylate cyclase (sGC) using rats model. Hyperglycemia was induced by intraperitoneal injection of streptozotocin in young (9wks), middle aged (54wks) and elderly (108 wks) male wister rats. After 1 to 12 weeks of hyperglycemia induction, rats were sacrificed and NO related responses and molecular analyses were investigated in thoracic aortas. The fasting blood glucose was increased 340±13 mg/dl in hyperglycemic induced rats. NO stimulated and basal responses were not significantly changed in younger (9wks.) rats when they were slightly decreased under hyperglycemia for more than 9 weeks. Endothelium independent response by nitroglycerin was diminished in elderly rats (108 wks) as compared with those in younger and middle aged rats (54 wks). Further, it was diminished in status of hyperglycemia for longer than 4 weeks. NO stimulated and basal responses were slightly decreased in aortas of elderly rats, and significantly decreased in hyperglycemia and depending on the duration of hyperglycemia. eNOS and soluble guanylate cyclase protein tended to decrease in aged diabetic rats. Further, O_2^- was increased by aging and hyperglycemia.

我们试图利用血管内分泌系统（瓜氨酸-精氨酸循环）治疗晚期动脉粥样硬化。本研究还探讨了诱导型一氧化氮合酶（iNOS）和可溶性鸟苷酸环化酶在老年晚期动脉粥样硬化动物模型中的作用。首先，我们观察了家兔动脉粥样硬化晚期T细胞和巨噬细胞中iNOS和ONOO^-的表达。应用L-精氨酸而不是瓜氨酸可延缓动脉粥样硬化的进展。第二，采用大鼠模型，测定内皮和非内皮血管反应、eNOS和可溶性鸟苷酸环化酶（sGC）。用链脲佐菌素（STZ）腹腔注射法建立青年（9周龄）、中年（54周龄）和老年（108周龄）雄性Wister大鼠高血压模型。在高血糖诱导1至12周后，处死大鼠，并在胸部动脉瘤中研究NO相关反应和分子分析。高血糖大鼠空腹血糖升高340±13 mg/dl。NO刺激和基础反应在年轻（9周）没有显着变化。大鼠在高血糖状态下持续9周以上，与中青年大鼠（54周）相比，老年大鼠（108周）对硝酸甘油的内皮非依赖性反应减弱。此外，高血糖状态持续时间超过4周。NO刺激反应和基础反应在老年大鼠睾丸中略有降低，在高血糖时显著降低，并依赖于高血糖的持续时间。eNOS和可溶性鸟苷酸环化酶蛋白在老年糖尿病大鼠有下降趋势。衰老和高血糖使O_2^-增加。