摘要
详细介绍了茶多酚保护脑神经防止PD损伤作用及其分子机理.家族遗传虽然是帕金森病(PD)的重要因素,但主要与环境因素有关(大约70%),其中氧化应激在致病机理中发挥着重要作用.茶多酚的抗氧化作用和及饮后可以进入血液甚至穿越血脑屏障为其保护脑神经防止PD提供了重要条件.在细胞水平,选择6-OHDA诱导的PC12和SH-SY5Y细胞作为细胞模型,结果表明,茶多酚预处理可明显减少细胞的凋亡率,防止线粒体膜电位下降,降低细胞内活性氧和钙离子累积.茶多酚还可以抑制6-OHDA诱导NO升高和nNOS与iNOS过量表达,降低细胞内蛋白质结合硝基酪氨酸水平.在动物水平,利用6-OHDA建立PD大鼠模型,探讨茶多酚对其保护作用机制.结果发现,茶多酚可以浓度和时间依赖性减轻6-OHDA诱导产生的旋转行为,降低中脑和纹状体中ROS和NO含量、脂质过氧化程度、硝酸盐/亚硝酸盐含量、蛋白质结合硝基酪氨酸浓度,同时降低nNOS和iNOS表达水平.茶多酚预处理可增加黑质致密部存活神经元,减少凋亡细胞.上述实验结果证明,口服茶多酚可以有效保护脑组织免于6-OHDA损伤引起的神经细胞死亡,其保护作用可能是通过ROS和NO的途径减少过氧亚硝基的生成实现的.
About 70% of Parkinson's pathogenesis comes from environment factor and one important of which is oxidative stress although the genetic factor plays an important role. The antioxidant of green tea polyphenols(GTP) and they can enter into plasma even penetrate blood brain barie provides an important condition for the protective effects of GTP against Parkinson's Disease(PD). In cellular model the protective mechanisms of GTP on PC12 and SH-SY5Y cells against apoptosis induced by 6-hydroxydopamine (6-OHDA) were investigated. GTP attenuated 6-OHDA-induced early apoptosis, prevented the decrease in mitochondrial membrane potential, suppressed accumulation of reactive oxygen species (ROS) and of intracellular free Cav. GTP also counteracted 6-OHDA-induced nitric oxide increase and over-expression ofnNOS and iNOS, and decreased the level of protein bound 3-Nitro-tyrosine (3-NT). Using PD rat model injected by 6-OHDA, the effect of GTP were investigated on animal model. Results showed that GTP attenuated the injury in a dose and time dependent manner. Pretreatment of the animals with GTP decreased ROS and NO production, thiobarituric acid reactive substances content, nitrite/nitrate concentration, and protein bound 3-Nitro-tyrosine (3-NT) in brain homogenate of midbrain and striatum in a concentration and time dependent manner. NOS participated in the neuron death induced by 6-OHDA and it was found that the pretreatment with GTP could decrease the protein level of nNOS and iNOS. More neurons survived and less cells suffered apoptosis in the substantia nigra pars compacta (SNc) of GTP treated animal brain. These results suggest that oral administration of GTP increases the antioxidant level in the brain and protects the brain against cell death caused by 6-OHDA. The experimental results of present study support the neuroprotection of GTP and provided new strategy of preventing and curing Parkinson's diseases by ROS-NO pathway.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2008年第7期735-743,共9页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(110200101056)
国家重点基础研究发展计划(973)(2006CB500706)资助项目~~
关键词
帕金森病
茶多酚
自由基
天然抗氧化剂
Parkinson's disease, green tea polyphenols, free radicals, natural antioxidant