Beneficial effects and mechanisms of long-term voluntary exercise on stroke events in stroke-prone spontaneously hypertensive rats

长期自主运动对脑卒中易发性高血压大鼠脑卒中事件的有益作用及机制

基本信息

批准号：
17500489
负责人：
NIWA Atsuko
金额：
$ 2.46万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Epidemiological studies have showed that physical exercise reduced the risk of cardiovascular disease, but the mechanisms are not clear. This study planned to examine how a long-term and moderate exercise affected on the stroke events caused by vascular endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP at pre-hypertensive stave were allowed to run voluntarily in a wheel for 8 wks (EX). Sedentary rats were placed in the cage without running (SE).EX rats decreased only slightly systolic blood pressure compared with SE, and reduced the incidence of stroke and mortality. In aortas of EX, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels, eNOS activity and NO production were elevated compared with those SE. Whereas, expression of Nox1 and Nox4, NADPH oxidase components, the activity and superoxide production were lower in aortas of EX than SE. EX rats showed lower serum levels of inflammatory cytokines and chemokines. Furthermore, arterial thickening and collagen contents was attenuated in EX than SE.In aortas of EX, the phosphorylation of MAPKs, ERK1/2, JNK and p38 MAPK, and activating transcription factors of AP-1 and NF-kB were decreased. EX weakened macrophage infiltration and NF-kB-triggered inflammatory responses in cerebral lesion compared with SE. In conclusion, the beneficial training effect is closely related to increase in Akt-dependent eNOS activation and decrease in oxidative stress, and then mitigate the inflammation associated with hypertension in the vessels and ischemic changes in the brain even in genetic hypertensive animals with stroke risk.

流行病学研究表明，体育锻炼降低了心血管疾病的风险，但这些机制尚不清楚。这项研究计划研究由易于自发的高血压大鼠（SHRSP）引起的长期和中等运动对中风事件的长期和中等运动。墨西哥前座椅的SHRSP被允许在车轮中自愿运行8周（EX）。与SE相比，将久坐的大鼠置于笼子中。EX大鼠仅降低了略微收缩的血压，并降低了中风和死亡率的发生率。在EX的主动脉中，与SE相比，磷酸化的AKT和内皮一氧化氮合酶（ENOS）水平，ENOS活性和无生产升高。尽管NOX1和NOX4的表达，NADPH氧化酶成分，而EX的主动脉中的活性和超氧化物的产生低于SE。 EX大鼠的炎性细胞因子和趋化因子的血清水平较低。此外，在EX的主动脉，ERK1/2，JNK和P38 MAPK的磷酸化中，动脉增厚和胶原蛋白含量被衰减。与SE相比，前巨噬细胞浸润和NF-KB触发反应的巨噬细胞浸润和NF-KB触发的反应。总之，有益的训练效果与依赖Akt依赖的eNOS激活和氧化应激的减少密切相关，然后减轻血管中与高血压相关的炎症，即使在患有中风风险的基因高血压动物中，大脑中的缺血性变化也是如此。