自由基、天然抗氧化剂与神经退行性疾病  

Free Radicals, Natural Antioxidants and Neurodegenerative Disease

作　　者：赵保路[1] 

机构地区：[1]中国科学院生物物理研究所,脑与认知国家重点实验室,北京100101

出　　处：《生物物理学报》2010年第4期263-274,共12页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(29935080);"973"项目(2006CB500700)~~

摘　　要：神经退行性疾病,老年痴呆症(Alzheimer's disease,AD)、帕金森症(Parkinson'sDisease,PD)和中风(脑卒中)严重危害老年人的身体健康和生活质量。这些疾病的发病机制目前尚不完全清楚,也无有效治疗方法。目前的研究发现,氧化应激产生的活性氧和NO自由基在诱导细胞的凋亡和导致神经退行性疾病AD、PD和中风方面发挥了重要作用。该文章综述了神经退行性疾病的自由基机理和天然抗氧化剂对这些疾病的预防和治疗作用机理。天然抗氧化剂,如茶多酚,能够防止6-羟多巴胺(6-hydroxydopamine,6-OHDA)诱导的细胞凋亡,保护线粒体功能从而预防6-OHDP诱导大鼠的PD症状;大豆异黄酮和尼古丁作为抗氧化剂可以防止Amyloid-β(Aβ)诱导的海马细胞凋亡和转基因小鼠脑中Aβ的沉积,抑制6-OHDA诱导细胞凋亡过程线粒体细胞色素C释放。在转基因鼠海马CA1区的Aβ斑中,铜、铁浓度比周围神经明显增高,用尼古丁处理明显减少海马CA1区Aβ斑及其周围神经中铜和铁的浓度,尼古丁可以抑制分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)的激活,核因子-κB(Nuclear factor kappa B,NF-κB)和致癌基因蛋白(Myc codes for a protein that binds to theDNA of other genes,C-Myc)的活化,使一氧化氮合酶和一氧化氮生成下调,尼古丁介导的神经信号通路过程受乙酰胆碱受体(acetylcholine receptor,α7nAChRs)调控。研究还发现山楂黄酮通过抑制活性氧和调节一氧化氮自由基可以预防和治疗中风。这些结果为神经退行性疾病的基础理论研究和临床实践提供了新的思路和实验依据。The neurodegenerative diseases, Alzheimer＇s disease （AD）, Parkinson＇s disease （PD） and stroke seriously affect the health and life quality, which are becoming a social problem. The pathogenesis of these diseases is not clear and there is no effective method to cure them. The free radical mechanism for neurodegenerative diseases, prevention and curative mechanisms of natural antioxidants against these diseases are reviewed in this paper. Reactive oxygen species （ROS） and NO free radicals generated from oxidative stress play an important role in the pathogenesis of AD, PD and stroke. Natural antioxidant drugs not only can cure the disease but also can enhance immunological responses of the patient leading to better health. For example, green tea polyphenols （GTP） can prevent 6-OHDA-induced cell apoptosis, stabilize mitochondrial membrane potential, suppress accumulation of ROS and of intracellular free Ca 2＋, prevent the animals against 6-OHDA induced PD symptoms. Experiment results also show that soy genestien and nicotine are benifical for PD and AD and studies show that nicotine can inhibit cytochrome C release from mitochondria induced by 6-OHDA/MPP＋; nicotine can protect neuron against apoptosis induced by β-amyloid peptide; nicotine can inhibit β-amyloid deposit in brain; nicotine inhibit cupper and zinc deposit in the brain and nicotine can prevent neurodegenerative diseases by inhibiting NF-κB, nitric oxide synthase expression and NO generation through nAChRs, MAPK and C-Myc pathway. It was also found that Crataegus flavone protects neuron cells against ischemia/reperfusion brain damage in Mongolian gerbils. These results provide new insight for explaining the mechanisms of pathology of neurodegenerative diseases and neuroprotective effects of natural antioxidants.

关 键 词：自由基 天然抗氧化剂 神经退行性疾病 帕金森症 老年痴呆症 中风 

分 类 号：Q493[生物学—生理学]