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，体育锻炼可以降低心血管疾病的风险，但其机制尚不清楚。本研究计划探讨长期适度运动对易发生中风的自发性高血压大鼠（SHRSP）血管内皮功能障碍引起的中风事件有何影响。高血压前期的 SHRSP 被允许在轮子上自愿运行 8 周（EX）。将久坐的大鼠放置在笼子中而不跑步（SE）。与SE相比，EX大鼠的收缩压仅略有下降，并降低了中风和死亡率。在 EX 的主动脉中，与 SE 相比，磷酸化 Akt 和内皮一氧化氮合酶 (eNOS) 水平、eNOS 活性和 NO 产生升高。而 EX 主动脉中 Nox1 和 Nox4 的表达、NADPH 氧化酶成分、活性和超氧化物产量均低于 SE。 EX 大鼠的血清炎症细胞因子和趋化因子水平较低。此外，EX的动脉增厚和胶原含量比SE减弱。在EX的主动脉中，MAPKs、ERK1/2、JNK和p38 MAPK的磷酸化以及AP-1和NF-kB的激活转录因子减少。与 SE 相比，EX 减弱了脑病灶中的巨噬细胞浸润和 NF-kB 引发的炎症反应。总之，有益的训练效果与 Akt 依赖性 eNOS 激活的增加和氧化应激的减少密切相关，从而减轻与血管高血压和大脑缺血性变化相关的炎症，甚至在具有中风风险的遗传性高血压动物中也是如此。