eNOS在运动训练改善高血压大鼠认知障碍中的作用与机制

慢性高血压是认知障碍的常见原因。近来发现脑内Aβ异常沉积与高血压导致的认知障碍密切相关，且血管内皮损伤是Aβ异常沉积的关键，但其具体机制未明。我们前期研究发现运动训练可:①增加脑梗死大鼠脑内IGF-1的表达,激活Akt通路;②促进高血压大鼠脑内eNOS表达,减少Aβ沉积,改善认知功能。而eNOS是主要的血管内皮保护物质,Akt通路在调节eNOS表达中起重要作用。据此我们提出,调节eNOS表达进而保护血管内皮可能是运动训练减少高血压引起Aβ沉积的主要机制。本研究以运动训练作为干预手段,采用RNA干扰、抗AβIgG注射等方法,明确eNOS表达对慢性高血压大鼠脑内Aβ沉积及认知障碍的影响,并检测Aβ沉积的来源及 IGF-1/PI3K/Akt通路在其中的作用,旨在探讨eNOS在运动训练改善高血压所致认知障碍中的作用及其通路。研究结果将对阐明高血压所致认知障碍的发病机制及优化其防治策略具有重要意义。

Hypertension is an important reason for cognitive impairment. Recently, β-amyloid(Aβ) deposition is considered the key step in hypertension induced cognitive impairment. It is demonstrated that endothelium dysfunction contributes to Aβ deposition under the condition of hypertension, but the underling mechanism is unclear. In our previous study, we demonstrated that exercise activated Akt pathway and promoted IGF-1 expression in rat model with cerebral infarction, up-regulated endothelial nitric oxide synthase (eNOS) and decreased Aβ deposition, then improved cognitive dysfunctionin in hypertensive rats. Akt pathway activated by exercise up-regulates eNOS expression, which plays critical role in endothelial protection. Therefore, we propose that eNOS may involve in Aβ burden decreasing and cognitive function improvement under the condition of hypertension. In order to identify the role of eNOS expression in Aβ deposition and cognitive function in chronic hypertensive rats, we will adopt physical exercise as an intervene measure, RNA interference, as well as Aβ antibodies injection. Furthermore, we will detect the source of Aβ deposition in brain of hypertensive rats and the effect of IGF-1/PI3K/Akt athway. The results may provide a new direction for exercise improved cognitive dysfunction in hypertension, and contribute to further understand the pathogenesis, optimize clinical prevention and therapy of cognitive dysfunction in hypertension.