MCI-186对Aβ25-35诱导PC12细胞晚期糖基化终产物的影响(2)
糖的醛基和蛋白质的氨基之间也可以进行非酶糖基化反应，生成不可逆的AGEs[7]。蛋白质一旦被AGEs修饰, 即丧失其生理功能。AGEs除直接使蛋白成分相互交联、DNA畸变外，还通过促使Aβ生成、促进氧化应激反应、上调AGEs结合受体(RAGE)表达等机制, 导致AD的发生。因此，神经元中活性羰基化合物的生成会使AD脑内AGEs增多，这种羰基状态除加速神经元功能障碍外，也会增加AD发病的易感性[8]。
研究证实，MCI-186作为一种新型的自由基清除剂，能够通过清除·OH而发挥其神经保护作用。在缺血-再灌注动物模型中也发现，MCI-186在再灌注早期尚能改善缺血诱导的海马齿状回突触长时程增强，提示MCI-186能改善学习记忆能力[9]。本研究通过给予MCI-186预保护PC12细胞，再给予Aβ25-35对细胞进行干预，结果显示该组PC12细胞生存率比未用MCI-186保护的细胞生存率明显升高，AGEs的生成也较未用MCI-186保护的细胞生成的要明显减少，进一步证实MCI-186能够起到保护神经细胞的作用。本研究认为MCI-186能够清除Aβ产生的·OH而达到保护神经细胞的目的。
[参考文献]
[1]Ding Q, Dimayuga E, Keller JN. Oxidative damage, protein synthesis, and protein degradation in Alzheimer's disease [J]. Curr Alzheimer Res， 2007，4(1):73-79.
[2]Christen Y. Oxidative stress and Alzheimer disease[J]. Am J Clin Nutr, 2000, 71(2): s621-s629.
[3]Polidori MC. Oxidative stress and risk factors for Alzheimer's disease: clues to prevention and therapy[J]. J Alzheimers Dis, 2004, 6(2): 185-191.
[4]Varadarajan S, Yatin S, Aksenova M,et al.Alzheimer's amyloid beta-peptide- associated free radical oxidative stress and neurotoxicity[J]. J Structural Biol 2000; 130 (2-3):184-208.
[5]罗南萍, 胡成进. 阿尔茨海默病与血管性痴呆的实验室研究进展[J].中国临床康复, 2004, 8(25): 5338-5340.
[6]Luth HJ, Ogunlade V, Kuhla B,et al.Age-and stage-dependent accumulation of advanced glycation end products in intracellular deposits in normal and Alzheimer's disease brains[J]. Cereb Cortex, 2005, 15(2): 211-220.
[7]Yamagishi S, Nakamura K, Matsui T,et al. A novel pleiotropic effect of atorvastatin on advanced glycation end product (AGE)-related disorders[J]. Med Hypotheses，2007，69(2):338-340.
[8]黄树其, 黄流清. 糖化终末产物与阿尔茨海默病[J]. 国外医学老年医学分册, 2003, 24(4): 180-183.
[9]Otani H, Togashi H, Jesmin S,et al.Temporal effects of edaravone, a free radical scavenger,on transient ischemia-induced neuronal dysfunction in the rat hippocampus [J]. Eur J Pharmacol,2005,512(2-3):129-137.
(收稿日期：2007-11-02), http://www.100md.com(李慧子 于 明)
研究证实，MCI-186作为一种新型的自由基清除剂，能够通过清除·OH而发挥其神经保护作用。在缺血-再灌注动物模型中也发现，MCI-186在再灌注早期尚能改善缺血诱导的海马齿状回突触长时程增强，提示MCI-186能改善学习记忆能力[9]。本研究通过给予MCI-186预保护PC12细胞，再给予Aβ25-35对细胞进行干预，结果显示该组PC12细胞生存率比未用MCI-186保护的细胞生存率明显升高，AGEs的生成也较未用MCI-186保护的细胞生成的要明显减少，进一步证实MCI-186能够起到保护神经细胞的作用。本研究认为MCI-186能够清除Aβ产生的·OH而达到保护神经细胞的目的。
[参考文献]
[1]Ding Q, Dimayuga E, Keller JN. Oxidative damage, protein synthesis, and protein degradation in Alzheimer's disease [J]. Curr Alzheimer Res， 2007，4(1):73-79.
[2]Christen Y. Oxidative stress and Alzheimer disease[J]. Am J Clin Nutr, 2000, 71(2): s621-s629.
[3]Polidori MC. Oxidative stress and risk factors for Alzheimer's disease: clues to prevention and therapy[J]. J Alzheimers Dis, 2004, 6(2): 185-191.
[4]Varadarajan S, Yatin S, Aksenova M,et al.Alzheimer's amyloid beta-peptide- associated free radical oxidative stress and neurotoxicity[J]. J Structural Biol 2000; 130 (2-3):184-208.
[5]罗南萍, 胡成进. 阿尔茨海默病与血管性痴呆的实验室研究进展[J].中国临床康复, 2004, 8(25): 5338-5340.
[6]Luth HJ, Ogunlade V, Kuhla B,et al.Age-and stage-dependent accumulation of advanced glycation end products in intracellular deposits in normal and Alzheimer's disease brains[J]. Cereb Cortex, 2005, 15(2): 211-220.
[7]Yamagishi S, Nakamura K, Matsui T,et al. A novel pleiotropic effect of atorvastatin on advanced glycation end product (AGE)-related disorders[J]. Med Hypotheses，2007，69(2):338-340.
[8]黄树其, 黄流清. 糖化终末产物与阿尔茨海默病[J]. 国外医学老年医学分册, 2003, 24(4): 180-183.
[9]Otani H, Togashi H, Jesmin S,et al.Temporal effects of edaravone, a free radical scavenger,on transient ischemia-induced neuronal dysfunction in the rat hippocampus [J]. Eur J Pharmacol,2005,512(2-3):129-137.
(收稿日期：2007-11-02), http://www.100md.com(李慧子 于 明)