摘要
心血管疾病具有很高的发病率和致死率。近年来研究显示,一氧化氮合酶(NOS)解偶联与心血管疾病密切相关。四氢生物蝶呤(BH4)是NOS作用的重要辅因子,催化L-精氨酸生成一氧化氮。BH4缺乏能导致NOS解偶联,使一氧化氮合成减少及活性氧生成增加。一氧化氮是调节血管舒张功能的重要因子,而大量氧自由基能导致氧化应激,损伤血管内皮功能,促进多种心血管疾病的发生、发展,如高血压病、动脉粥样硬化、心肌肥厚、糖尿病、心律失常等。BH4的生物利用度由从头合成和再循环共同决定,然而,当BH4/NOS或BH4/二氢生物蝶呤(BH2)比例失调时,可导致NOS解偶联,加重氧化应激,形成恶性循环。外源性补充或增加内生BH4水平,能增加一氧化氮的生物利用度及改善血管内皮功能。因此,深入了解BH4与心血管疾病的关系,对心血管疾病的防治具有重要作用。
Cardiovascular diseases have a high morbidity and mortality. Recent studies have shown that nitric oxide synthase （NOS） uncoupling is closely related with cardiovascular disease. Tetrahydrobiopterin （BH4） is an important cofactor of NOS function, and can catalyze L-catalytic arginine to produce nitric oxide. BH4 deficiency can lead to NOS uncoupling, causing the decrease of nitric oxide synthesis and the increase of reactive oxygen species generation. Nitric oxide is an important factor in regulating vascular dias- tolic function,but a large amount of oxygen free radicals can cause oxidative stress, and injure endothelial function, promoting the occurrence and development of many cardiovascular diseases, such as hypertension, atherosclerosis, myocardial hypertrophy, diabetes, cardiac arrhythmia and so on. BH4 bioavailability is deter- mined by a balance of enzymatic de novo synthesis and recycling. However,when the ratio of BH4/NOS or BH4/tetrahydrobiopteritl（ dihydrobiopterin BH2） is imbalanced,it can cause NOS uncoupling,increase oxi- dative stress and form a vicious circle. The supplement of exogenous or increase of endogenous BH4 level, can increase the bioavailability of nitric oxide and improve vascular endothelial function. Therefore, in-depth understanding of the relationship between BH4 and cardiovascular disease, plays an important role in the pre- vention and treatment of cardiovascular diseases.
出处
《医学综述》
2015年第22期4061-4064,共4页
Medical Recapitulate
关键词
心血管疾病
四氢生物蝶呤
一氧化氮合成酶
Cardiovascular diseases
Tetrabydrobiopterin
Nitric oxide synthase
