四氢生物蝶呤在高血压和高同型半胱氨酸对脑卒中协同作用中的研究

项目名称： 四氢生物蝶呤在高血压和高同型半胱氨酸对脑卒中协同作用中的研究

项目编号： No.81200187

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 董一飞

作者单位： 南昌大学

项目金额： 23万元

中文摘要： 中国高血压人群脑卒中发生率明显高于欧美国家，高血压发生率和治疗因素都不能充分解释我国与欧美国家的这种差异。血浆同型半胱氨酸（Hcy）是脑卒中的一个重要危险因素，我国高血压人群伴有Hcy升高的比例显著高于欧美国家。高血压合并高Hcy患者血管疾病风险显著升高，这种协同作用在中国人群中突出表现在当高血压合并Hcy升高时，脑卒中发生危险显著增加。我们的前期研究表明四氢生物蝶呤（BH4）通过调节一氧化氮合酶（NOS）脱偶联显著改善高血压血管内皮功能损害。同时研究也表明高Hcy通过BH4调节NOS脱偶联机制降低组织一氧化氮生物利用度同时升高氧化应激水平。因此我们推测：①高血压和高Hcy协同作用于BH4，调节NOS脱偶联介导的氧化应激机制，显著增加脑卒中发生；②高血压合并高Hcy患者外周循环BH4水平与其脑卒中呈相关关系。该研究能为高血压和高Hcy对脑卒中协同作用机制的研究提供重要的基础和临床实验数据。

中文关键词： 高血压；高同型半胱氨酸；内皮功能；脑卒中；氧化应激

英文摘要： Stroke incidence in Chinese hypertensive population is significantly higher than that in western countries. The incidence and treatment strategy of hypertension in China cannot adequately explain such a difference. Hyperhomocysteinemia (HHcy) is regarded as a risk factor for stroke and the incidence of HHcy in hypertensive patients is significantly higher in China than that in western countries. The risk of vascular diseases is significantly increased in hypertensive patients accompanied with HHcy which, in China, is particularly represented as a significant high stroke incidence in those patients. We have reported that tetrahydrobiopterin (BH4) is involved in hypertensive vascular dysfunction by regulating nitric oxide synthase (NOS) uncoupling-mediated oxidative stress. Meanwhile, BH4 has also been reported to be involved in HHcy-induced vascular dysfunction and oxidative stress. We thus hypothesize that (1) BH4 is involved in the synergistic effect of hypertension and HHcy on stroke by regulating NOS uncoupling-mediated oxidative stress; (2) BH4 concentration in peripheral circulation correlates with stroke in hypertensive patient accompanied with HHcy. This work may provide novel mechanisms for the synergistic effect of the hypertension and HHcy on stroke.

英文关键词： hypertension；hyperhomocystinemia；endothelial function；stroke；oxidative stress