Xiao X Q, Wang R, Tang X C
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
J Neurosci Res. 2000 Sep 1;61(5):564-9. doi: 10.1002/1097-4547(20000901)61:5<564::AID-JNR11>3.0.CO;2-X.
Increased oxidative stress resulting from free radical damage to cellular function is associated with a number of neurodegenerative diseases, in particular with Alzheimer's disease (AD). The deposition of amyloid beta-peptide (Abeta), the major pathological hallmark for AD, has been suggested as the central disease-causing and disease-promoting event for the disease, and the pathological role of Abeta was partially mediated by oxidative stress. Here we compared the effects of huperzine A (HupA) and tacrine, two acetylcholinesterase (AChE) inhibitors available for AD, on Abeta-induced cell lesion, level of lipid peroxidation, and antioxidant enzyme activities in rat PC12 and primary cultured cortical neurons. Following exposure of both cells to different concentrations of an active fragment of Abeta, a marked reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased production of malondialdehyde (MDA) and superoxide dismutase (SOD), were observed. Pretreatment of the cells with HupA or tacrine (0.1-10 microM) prior to Abeta exposure significantly elevated the cell survival and GSH-Px and CAT activities and decreased the level of MDA. Both drugs have similar protection against Abeta insult. Our results indicate that HupA and tacrine exert neuroprotective effects against Abeta toxicity, which might be of importance and might contribute to their clinical efficacy for the treatment of AD.
自由基对细胞功能造成损伤导致氧化应激增加，这与许多神经退行性疾病相关，尤其是与阿尔茨海默病（AD）有关。淀粉样β肽（Aβ）沉积是AD的主要病理标志，被认为是该疾病的核心致病和促病事件，且Aβ的病理作用部分由氧化应激介导。在此，我们比较了石杉碱甲（HupA）和他克林这两种可用于治疗AD的乙酰胆碱酯酶（AChE）抑制剂，对Aβ诱导的大鼠嗜铬细胞瘤（PC12）细胞损伤、脂质过氧化水平以及抗氧化酶活性的影响。在将两种细胞暴露于不同浓度的Aβ活性片段后，观察到细胞存活率、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）活性显著降低，丙二醛（MDA）和超氧化物歧化酶（SOD）生成增加。在Aβ暴露前用HupA或他克林（0.1 - 10 microM）预处理细胞，可显著提高细胞存活率以及GSH-Px和CAT活性，并降低MDA水平。两种药物对Aβ损伤具有相似的保护作用。我们的结果表明，HupA和他克林对Aβ毒性具有神经保护作用，这可能具有重要意义，并可能有助于它们治疗AD的临床疗效。
