Department of Respiratory, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6999-7012. doi: 10.26355/eurrev_201810_16171.
Grape seed proanthocyanidin extract (GSPE), as one of the most popular natural drug extracted from the grape, has been reported to improve endothelial function and arteriosclerosis. However, little is known about the influence of GSPE on hypertension and vascular remodeling. Profilin-1, an Actin-binding protein, is closely involved in the remodeling of large vessels in ouabain-induced hypertension. To date, there is no effective prevention or treatment in place for the high incidence of ischemic stroke associated with hypertension. In this study, we aimed to determine the role of GSPE via inhibition Profilin-1 in ischemic cerebral cortices of ouabain-hypertension rats and potentially provide a new target to prevent stroke associated with hypertension.
The blood pressure of male Sprague-Dawley (SD) rats was measured during a period of ouabain-induced hypertension. The expression of Profilin-1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the cerebral cortex were determined by quantitative Real Time-PCR (qRT-PCR) and Western blot. Histopathological and behavioral tests were also conducted.
Blood pressure elevation started at week 5 and reached clinical standards for hypertension at week 8. GSPE was proved to suppress Profilin-1 and VEGF levels through inhibition of Profilin-1-protein kinase B (AKT)-hypoxia inducible factor-1α (HIF-1α) signal pathway and promote eNOS expression. Moreover, the histopathological and ethiological improvement was observed in GSPE over-expression and Profilin-1 inhibition groups.
We detected that GSPE could improve cerebral vascular damage through inhibiting Profilin-1 in an ouabain-induced hypertension model.
葡萄籽原花青素提取物（GSPE）作为从葡萄中提取的最受欢迎的天然药物之一，已被报道可改善内皮功能和动脉硬化。然而，关于 GSPE 对高血压和血管重构的影响知之甚少。丝状蛋白-1（Profilin-1）是一种肌动蛋白结合蛋白，它与哇巴因诱导的高血压中大血管的重构密切相关。迄今为止，尚无有效的预防或治疗措施可用于预防与高血压相关的缺血性中风的高发病率。在这项研究中，我们旨在通过抑制 Profilin-1 来确定 GSPE 在哇巴因诱导的高血压大鼠缺血性大脑皮质中的作用，并为预防与高血压相关的中风提供新的靶点。
在哇巴因诱导高血压期间测量雄性 Sprague-Dawley（SD）大鼠的血压。通过定量实时 PCR（qRT-PCR）和 Western blot 测定大脑皮质中 Profilin-1、血管内皮生长因子（VEGF）和内皮型一氧化氮合酶（eNOS）的表达。还进行了组织病理学和行为学测试。
血压升高始于第 5 周，第 8 周达到高血压临床标准。GSPE 被证明通过抑制 Profilin-1-蛋白激酶 B（AKT）-缺氧诱导因子-1α（HIF-1α）信号通路抑制 Profilin-1 和 VEGF 水平，并促进 eNOS 表达。此外，在 GSPE 过表达和 Profilin-1 抑制组中观察到组织病理学和病因学改善。
我们发现在哇巴因诱导的高血压模型中，GSPE 可通过抑制 Profilin-1 改善脑血管损伤。
