活性氧的生成与健康和疾病关系研究进展

Advances in Generation of Reactive Oxygen Species Associated with Health and Diseases

从历史上看,活性氧(reactive oxygen species,ROS)被认为只引起细胞损伤及生理功能障碍,ROS及其氧化损伤与多种疾病,包括神经退行性疾病、糖尿病、癌症和过早衰老相关。然而,近年来,越来越多的证据显示,ROS对健康至关重要。在生理条件下,低水平ROS的生成被认为是信号分子。另一方面,ROS的过度生成,与ROS缓冲系统的功能障碍相关,会导致慢性疾病的发展。因此,ROS的慢性释放参与许多疾病的发病。而且,ROS生成过量诱导生物分子的氧化损伤,进而导致衰老、癌症和许多其他疾病。ROS已经参与100多种疾病的发生,包括威胁人类健康的重大疾病癌症、心血管疾病、糖尿病、神经退行性疾病(如帕金森病和阿尔茨海默病)、获得性免疫缺陷综合征、中风和衰老的发生。本文综述了氧的出现与需氧真核生物的进化、ROS的种类、ROS的生理病理多效性、机体内主要的ROS、ROS的生成与反应、ROS与线粒体氧化磷酸化、细胞凋亡、免疫防御和炎症、肿瘤等方面的最新进展,鉴于ATP和ROS对生命的重要性,提出,调控线粒体氧化磷酸化实现ATP与ROS生成的平衡将是健康的关键。

Historically, reactive oxygen species（ROS） are thought to exclusively cause cellular damage and physiological dysfunctions. The accumulation of ROS and oxidative damage has been linked to multiple pathologies, including neurodegenerative diseases, diabetes, cancer, and premature aging. Accumulating evidence in recent years suggests that ROS are critical for health. In physiological conditions, ROS are considered as a signaling molecule produced at low level and in a transient manner. On the other hand, over-production of ROS, associated with the dysfunction of ROS buffering systems, can lead to the development of chronic diseases. Thus, chronic ROS release participates in the occurrence of over 100 kinds of diseases, including major diseases that threaten human health, such as cancer, cardiovascular diseases, diabetes, neurodegenerative diseases（Parkinson＇s and Alzheimer＇s diseases）, acquired immune deficiency syndrome, stroke and aging. This paper reviewes the latest progress in the presence of oxygen on earth and the evolution of aerobic eukaryotic organisms, ROS types, physiological and pathological pleiotropy of ROS, the major ROS in the body, the generation and reactions of ROS, the association of ROS with mitochondrial oxidative phosphorylation, apoptosis, immune defense, inflammation and cancers. Given the importance of ATP and ROS to life, we propose that the balance between the generation of ATP and ROS by regulation of mitochondrial oxidative phosphorylation will be the key to human health.