Skeletal Muscle Microcirculation in Obese Zucker Rats

肥胖 Zucker 大鼠的骨骼肌微循环

• 批准号: 6770843
• 负责人: JEFFERSON C FRISBEE
• 金额: $ 25.84万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6770843
• 关键词: diabetes risk; diet therapy; disease /disorder model; exercise; gene expression; genetically modified animals; hypertension; laboratory rat; metabolic syndrome; metabolism disorder chemotherapy; microcirculation; nonhuman therapy evaluation; noninsulin dependent diabetes mellitus; nutrition related tag; obesity; peripheral blood vessel; striated muscles; tissue /cell preparation

DESCRIPTION (provided by applicant): Diabetes mellitus (DM) is increasingly widespread and is a risk factor for development of peripheral vascular disease, a debilitating condition impacting 60 million Americans. With the concomitant development of additional complicating factors, including obesity, hypertension and dyslipidemia, a multi-pathology state develops: the metabolic Syndrome X. The obese Zucker rat (OZR) provides an excellent model for examining the impact of Syndrome X on the peripheral microcirculation, as owing to chronic hyperphagia, OZR sequentially develop type II DM, hypertriglyceridemia, and moderate hypertension. However, the impact of these developing pathologies on peripheral microcirculatory structure and function remains unclear. The proposed experiments will employ multiple levels of spatial resolution, ranging from measurements of enzyme expression and activity, through isolated microvessels, to perfused skeletal muscle for the examination of the effects of development of Syndrome X on skeletal muscle blood flow. Subsequent to the determination of the temporal development of Syndrome X and the resulting alterations to the peripheral microcirculation, further experiments will determine the effectiveness of chronic exercise and treating the individual disease components of Syndrome X on the structure and function of the microcirculation. These experiments will employ the OZR model of Syndrome X to determine consequences of the development of multi-component pathology on altered: 1) skeletal muscle arteriolar reactivity, 2) structure of individual microvessels and microvascular networks, and 3) perfusion and performance of in situ blood-perfused skeletal muscle. The completion of the experiments proposed in this application will allow for a fuller, more integrated understanding of the microcirculatory complications associated with Syndrome X and the ability to ameliorate developing impairments in the Zucker rat than presently exists. It is the applicant's contention that this knowledge can only be effectively garnered by extracting multiple phenotypes, at numerous levels of resolution from individual rats exhibiting Syndrome X and under conditions where the manifestation of Syndrome X is manipulated experimentally. From this base, future experiments can be developed which will target specific sites of impairment and control for the prevention and amelioration of the microcirculatory impairments associated with this debilitating pathological condition.

描述（由申请人提供）：糖尿病（DM）越来越广泛，是发展周围血管疾病的危险因素，这是一种影响6000万美国人的衰弱状况。 With the concomitant development of additional complicating factors, including obesity, hypertension and dyslipidemia, a multi-pathology state develops: the metabolic Syndrome X. The obese Zucker rat (OZR) provides an excellent model for examining the impact of Syndrome X on the peripheral microcirculation, as owing to chronic hyperphagia, OZR sequentially develop type II DM, hypertriglyceridemia, and中度高血压。但是，这些发展的病理对外周循环结构和功能的影响尚不清楚。提出的实验将采用多种水平的空间分辨率，范围从酶表达和活性，通过孤立的微血管到灌注骨骼肌，以检查综合征X的发展对骨骼肌血流的影响。在确定综合征X的时间发育以及周围微循环的结果改变之后，进一步的实验将决定慢性运动的有效性，并治疗综合征X的个体疾病成分在微循环的结构和功能上。这些实验将采用综合征X的OZR模型来确定多组分病理学对改变的后果：1）骨骼肌小动脉反应性，2）单个微血管和微血管网络的结构，以及3）灌注和表现，灌注和表现在原位血液中渗透的骨骼骨骼肌肉中。本应用程序中提出的实验的完成将允许对与综合征X综合征相关的微循环并发症的更全面，更集成，并能够改善Zucker大鼠中发展障碍的能力。申请人的论点是，这种知识只能通过提取多种表型来有效地获得，这是在表现出综合征X的单个大鼠的大量分辨率下以及在实验中操纵综合征X的表现的条件下。从这个基础上，可以开发未来的实验，该实验将针对特定的损害和控制部位，以预防和缓解与这种衰弱的病理状况相关的微循环障碍。