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氧化应激:疾病病理学中的主要执行者、在精子DNA损伤中的作用及预防策略

Oxidative stress: Major executioner in disease pathology, role in sperm DNA damage and preventive strategies.

作者信息

Bisht Shilpa, Dada Rima

机构信息

Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.

Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India,

出版信息

Front Biosci (Schol Ed). 2017 Jun 1;9(3):420-447. doi: 10.2741/s495.

Abstract

Oxidative stress (OS) has been implicated in a wide array of diseases such as neurodegenerative disorders, autoimmune diseases, complex lifestyle diseases and cancer. OS is caused by an imbalance in production of Reactive Oxygen Species (ROS) and antioxidant defenses in the cell which results in the damage of cellular components, inactivate essential metabolic enzymes and disrupt signal transduction pathways. OS induces peroxidative damage to the sperm plasma membrane, DNA fragmentation in sperm nuclear/mitochondrial genome and causes dysregulation in levels of mRNAs/transcripts. OS induced sperm DNA damage is associated with male infertility, recurrent pregnancy loss (RPL), congenital malformations and high frequency of childhood disorders. OS induced pathologies are caused by endogenous and exogenous factors, majority of which, are modifiable. Antioxidant supplementation could help in relieving OS, however, its long-term usage may disrupt the intricate oxidation-reduction balance and  can lead to "Reductive Stress". Adoption of simple lifestyle interventions may relieve OS and can also aid in its management. This may improve overall quality of life (QOL) and can reduce prevalence of OS induced diseases.

摘要

氧化应激(OS)与多种疾病有关,如神经退行性疾病、自身免疫性疾病、复杂的生活方式疾病和癌症。OS是由细胞内活性氧(ROS)产生与抗氧化防御失衡引起的,这会导致细胞成分受损、使关键代谢酶失活并破坏信号转导通路。OS会诱导精子质膜发生过氧化损伤、精子核/线粒体基因组中的DNA片段化,并导致mRNA/转录本水平失调。OS诱导的精子DNA损伤与男性不育、复发性流产(RPL)、先天性畸形和儿童疾病的高发病率有关。OS诱导的病理状况是由内源性和外源性因素引起的,其中大多数是可改变的。补充抗氧化剂有助于缓解OS,然而,长期使用可能会破坏复杂的氧化还原平衡,并可能导致“还原应激”。采取简单的生活方式干预措施可能会缓解OS,也有助于对其进行管理。这可能会改善整体生活质量(QOL),并降低OS诱导疾病的患病率。

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