．７４０＂生物化学与生物物理进展Ｐｒｏｇ．Ｂｉｏｃｈｅｍ．Ｂｉｏｐｈｙｓ．２００８；３５∽
了一氧化氮的终产物硝酸盐／亚硝酸盐的产量．与阴性对照组相比，６．ＯⅧ）Ａ注射侧中脑和纹状体内硝酸盐／亚硝酸盐显著升高，并且具有时间依赖性．茶多酚预处理剂量和时间依赖性降低了中脑和纹状体内脑匀浆的硝酸盐／亚硝酸盐水平．同时，茶多酚预处理都使得对照侧中脑和纹状体内硝酸盐／亚硝酸盐水平显著下降，并且具有剂量和时间效应．
利用分子生物学技术检测发现，６－ＯＨＤＡ显著增加了中脑和纹状体内ｎＮＯＳ和ｉＮＯＳ的蛋白质表达，并且是具有时间依赖效应的．茶多酚预处理可以显著降低中脑和纹状体内的ｎＮＯＳ和ｉＮＯＳ的蛋白表达．ｉＮＯＳ在阴性对照组也有表达，但表达量比较低，可能是由于手术和灌胃刺激导致的．与阴性对照相比，６－ＯＨＤＡ可显著提高中脑和纹状体内蛋白结合硝基酪氨酸含量，并且在中脑内有时间依赖效应，可能是与中脑黑质致密部神经元的缺失有关．茶多酚可以剂量依赖性地降低蛋白质结合硝基酪氨酸含量．用免疫组化的方法标记ＴＨ阳性神经元是观察中脑黑质多巴胺能神经元变化的有效手段．对中脑黑质ＴＨ免疫活性的神经元用ＤＡＢ显色，在６－ＯＨＤＡ注射三周后，正常组的动物ＴＨ阳性神经元的数目比６－ＯＨＤＡ损伤一侧的多，表明６－ＯＨＤＡ对中脑的多巴胺能神经元有显著的损伤作用．而低剂量和高剂量茶多酚可以明显地保护多巴胺能神经元免受６－ＯＨＤＡ的毒害．在细胞凋亡过程中，细胞内ＤＮＡ内切酶被激活，降解基因组ＤＮＡ，断裂的ＤＮＡ碎片可以被ＴＵＮＥＬ试验特异性的检测，因此ＴＵＮＥＬ可以特异性检测凋亡细胞．结果显示，阴性对照组黑质致密部神经元没有特异性染色，６－ＯＨＤＡ注射后三周，几乎所有的ＳＮｃ区神经元都被特异性的着色，显示６－ＯＨＤＡ经前脑内侧束扩散到ＳＮｃ区，引起ＳＮｃ区多巴胺能神经元的大量凋亡，同时，在６－ＯＨＤＡ诱导凋亡的神经元中，部分神经纤维显示ＴＵＮ－ＥＬ阳性，这种现象表明，断裂的ＤＮＡ碎片在神经元中由胞体向神经纤维末端运输，是一种凋亡神经元特有的现象，进一步说明６－ＯＨＤＡ注射后神经元ＤＮＡ的断裂至少部分是由凋亡引起的．茶多酚预处理剂量依赖性减少切片中凋亡神经元的数卧切．
Ｗｅｉｎｒｅｂ等在ＭＰＴＰ诱导的ＰＤ小鼠模型中，ＭＰＴＰ可以导致脑黑质部多巴胺神经原丢失，用茶提取物（Ｏ．５１ｍｇ／ｋｇ）和茶多酚ＥＧＣＧ（２，１０ｍｇ／ｋｇ）预
处理可以显著防止这一损伤，ＥＧＣＧ还能阻止ＭＰＴＰ引起的抗氧化酶的应激变化．体外运用酶动力学方法，发现茶多酚在一定的浓度范围内对小鼠脑ＭＡＯ有明确的抑制作用，其作用机制为可逆的非竞争性抑制．结果表明，茶多酚能够降低ＭＰＴＰ处理的小鼠各个脑区的ＭＡＯ的活性卿¨．
归纳以上研究，我们可以用图２表示茶多酚保护神经细胞防止６－ＯＨＤＡ诱导ＰＤ损伤的分子机理．
＿趣．２Ａｈｙｐｏｔｈｅｔｉｃａｌｍｏｄｅｌｄｉａｇｒａｍｍｊｎｇｆｏｒｔｈｅｐｏｔｅｎｔｉａｌｔａｒｇｅｔｓｏｆｇｒｅｅｎｔｅａｐｏｌｙｐｈｅｎｏｌｓ（ＧＴＰ）ｏｒＥＧＣＧａｒｅｓｕｇｇｅｓｔｅｄｉｎｃｅｌｌｓｉｇｎａＵｎｇｐａｔｈｗａｙｓａｆｆｅｃｔｅｄｂｙ６－ＯＨＤＡ－ｉｎｄｕｃｅｄｏｘｉｄａｔｉｖｅｓｔｒｅｓｓ
图２茶多酚（ＧＴＰ）或者ＥＧＣＧ防止６－ＯＨＤＡ导致ＰＤ氧化损伤的靶位置和信号通路模型
①直接抑制６－ＯＨＤＡ导致ＰＤ氧化应激和清除ＲＯＳ；②抑制６－ＯＨＤＡ对ＰＫＣ和ＥＲＫＩ／２的激活作用及ＰＫＣ磷酸化；③抑制ＮＦ－ｋＢ向细胞核转移和抑制其活性；④调节细胞死亡和周期：⑤调节细胞内ＮＯ水平和抑制过氧亚硝基生成．
３．３茶多酚的抗氧化作用
茶多酚的这些保护神经防止帕金森病损伤作用与其抗氧化作用有着密切关系．一种抗氧化剂能否抗氧化和抗氧化效率如何，一个很重要的性质就是它对氧自由基的清除作用．我们系统研究了茶多酚
对不同体系氧自由基的清除作用．
茶多酚保护脑神经防止帕金森病损伤作用及其分子机理
作者：赵保路， ZHAO Bao-Lu
作者单位：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
刊名：
生物化学与生物物理进展
英文刊名：PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
年，卷(期)：2008,35(7)
被引用次数：8次
参考文献(35条)
1.Guo S H;Bezard E;Zhao B L Protective effect of green tea polyphenols on the SH-SYSY cells against 6-OHDA induced apoptosis through ROS-NO pathway[外文期刊] 2005(04)
2.Tachibana H;Koga K;Fujimura Y A receptor for green tea polyphenol EGCG[外文期刊] 2004(03)
3.Liu X;Miller M J;Joshi M S Accelerated reaction of nitric oxide with o2 within the hydrophobic interior of biological membranes[外文期刊] 1998(05)
4.Zhang Y;Dawson V L;Dawson T M Oxidative stress and genetics in the pathogenesis of Parkinson's disease[外文期刊] 2000(02)
5.Dawson T M;Dawson V L Neuroprotective and neurorestorative strategies for Parkinson's disease[外文期刊] 2002(07)
6.Petrucelli L;O'Farrell C;Lockhart P J Parkin protects against the toxicity associated with overexpression of mutant a-synuclein:proteasome dysfunction selectively affects catecholaminergic neurons[外文期刊] 2002(06)
7.Castaneda E;Fleming S;Paquette M A Assessment of recovery in the hemiparkinson rat:Drug-induced rotation is inadequate 2005(03)
8.Levites Y;Weiureb O;Maor G Green tea polyphenol(-)-epigailocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration 2002(06)
9.Nie G J;Cao Y L;Zhao B L Protective effects of green tea polyphenols and their major component,(-)-epigallocatechin-3-gallate(EGCG),on 6-hydroxyldopamine-induced apoptosis in PC12 cells 2002(02) 10.Meredith G E;Halliday G;Totterdell S A critical review of the development and importance of proteinaceous aggregates in animal models of Parkinson's disease:new insights into Lewy body formation 2004(01)
11.Nie G J;Jin C F;Cao Y L Distinct effects of tea catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells[外文期刊] 2002(01)
12.Ni Y C;Zhao B L;Hou J W Protection of cerebeilar neuron by Ginkgo-biloba extract against apoptosis induced by hydroxyl radicals[外文期刊] 1996(01)
13.Zhao B L The health effects of tea polyphenols and their anfioxidant mechanism[外文期刊] 2006(01)
14.Zhao B L Antioxidant effects of green tea polyphenols[期刊论文]-Chinese Science Bulletin 2003(04)
15.Zhao B L;Liu S L;Chen R S Scavenging effect of catechin on frec radicals studied by molecular orbital calculation 1992(01)
16.Chen L J;Yang X Q;Jiao H L Effect of Tea Catechins on the Change of Glutathione Levels Caused by Pb2+ in PC12 Cells[外文期刊] 2004(06)
17.Chen L J;Yang X Q;Jiao H L Tea Catechins protect against lead-induced ROS formation,mitochondriai dysfunction and calcium dysregulation in PC 12 cells[外文期刊] 2003(07)
18.Chen L J;Yang X Q;Jiao H L Tea catechins protect against Lead-induced cytotoxicity,lipid peroxidation,and membrane fluidity in HepG2 Cells[外文期刊] 2002(01)
19.Gao J T;Tang H R;Zhao B L The toxicological damagemem of gas phase cigarette smoke on cells and protective effect of green tea polyphenols[外文期刊] 2001(02)
20.Nie G J;Wei T T;Shen S R Polyphenol protection of DNA against damage[外文期刊] 2001(02)
21.Groves J T Peroxynitrite:reactive,invasive and enigmatic[外文期刊] 1999(02)
22.Tanaka Y;Engelender S;lgarashi S Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis[外文期刊] 2001(05)
23.Zhao B L;Guo Q;Xin W J Free radical scavenging by green tea polyphenols[外文期刊] 2001(01)
24.Guo Q;Zhao B L;Hou J W ESR study on the structure-antioxidant activiity relationship of tea catechins and their epimers[外文期刊] 1999(01)
25.Guo Q;Zhao B L;Li M F Studies on protective mechanisms of four components of green tea polyphenols (GTP) against lipid peroxidation in synaptosomes 1996(01)
26.赵保路;王建潮;侯京武茶多酚对过氧亚硝基氧化二甲基亚砜产生的甲基自由基的清除作用 1996
27.沈生荣;杨贤强;杨发军儿茶素抗氧化作用的协同增强效应[期刊论文]-茶叶科学 1993(02)
28.Zhao B L;Li X J;He R G Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals 1989(02)
29.Weinreb O;Mandel S;Amit T Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases[外文期刊] 2004(02)
30.Levites Y;Weinreb O;Maor G Green tea polyphenol(-)-epigalincatechin-3-gaUate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-ioduced dopaminergic neurodegeneration[外文期刊] 2001(07)
31.Guo S H;Yan J Q;Bezard E Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson's disease through inhibition of ROS-NO pathway[外文期刊] 2007(12)
32.Suganuma Wide distribution of 3H-(-)-epigallocateehin gallate,a cancer preventive tea polyphanol,in mouse tissue[外文期刊] 1998(08)
33.Lee S R;Sub S I;Kim S P Protective effects of the green tea polyphenol (2)-epigallocatechin gallate against hippocampal neuronal damage after transient global ischemia in gerbils[外文期刊] 2000(02)
34.Levitesa Y;Youdima M B H;Maorb G Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear
factor-kappaB (NF-κB) activation and cell death by tea extracts in neuronal cultures[外文期刊] 2000(01)
35.Levites Y;Amit T;Youdim M B Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol(-)-epigallocatechin-3-gallate neuroprotective action[外文期刊] 2002(34)
引证文献(8条)
1.李大祥.鲜殊.杨卫.宛晓春茶叶的神经保护作用研究进展[期刊论文]-茶叶科学 2011(2)
2.何玲玲.封锦芳.肖荣.余焕玲.麻微微.丁冰杰.苑林宏染料木黄酮对β淀粉样肽25-35介导的PC12细胞凋亡过程相关基因表达的影响[期刊论文]-中国食品卫生杂志 2011(2)
3.陶丽珍.陈建宗帕金森病和ROS-NO通路[期刊论文]-国际老年医学杂志 2010(6)
4.吴彬彰.赵阳.王剑清.叶卓明.张宝.李洪才茶多酚对外源性亚硝酸盐清除作用的研究[期刊论文]-癌变·畸变·突变 2010(6)
5.薛山.赵国华茶多酚生物学功效的研究现状及前景展望[期刊论文]-漳州师范学院学报（自然科学版） 2009(3)
6.马雪泷.吴孝兵.吴边茶多酚对蟾蜍坐骨神经干兴奋传导及骨骼肌收缩的影响[期刊论文]-资源开发与市场
2009(7)
7.梁俊玉.周纲.刘志杰.张继茶多酚对植物油抗氧化的研究与应用[期刊论文]-现代农业科技 2009(15)
8.吕志坤.邵蓓.张扬.宋兴伟.黄学荪.王群姬.徐惠琴.牛晓婷茶多酚对1-甲基-4-苯基-1-2-3-6-四氢吡啶帕金森病小鼠模型细胞因子的影响[期刊论文]-中国临床神经科学 2009(6)
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