山茱萸羟甲基糠醛对叠氮钠致神经细胞损伤的影响及其作用机制  

Effects and mechanisms of hydroxymethyl-furfural on nerve cell injury induced by sodium azide

作　　者：张如意[1] 朴景华[1] 张兰[1] 楚晋[1] 徐艳玲[1] 李林[1] 

机构地区：[1]首都医科大学宣武医院药物研究室,神经变性病教育部重点实验室,北京100053

出　　处：《中国药理学通报》2008年第11期1464-1469,共6页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究计划(973计划)资助项目(No2003CB517104);国家自然科学基金资助项目(No90709011,30472184);北京市自然科学基金资助项目(No7032013,7050001);北京市科技新星计划资助项目(NoH020821390190);首都医学科研发展基金资助项目(No2002-3002)

摘　　要：目的观察从山茱萸中提取的山茱萸羟甲基糠醛(HMF)对线粒体呼吸链复合体IV抑制剂叠氮钠致神经细胞损伤的保护作用,并探讨其作用机制。方法不同剂量的HMF分别与人神经母细胞瘤细胞系SH-SY5Y细胞预孵育24h,洗去培养液,加入50mmolL-1叠氮钠作用4h,用MTT法和乳酸脱氢酶(LDH)漏出率测定细胞存活率,激光共聚焦显微镜观察线粒体膜电位和细胞骨架(微管、微丝)结构,免疫细胞化学法检测β-淀粉样肽(Aβ)的表达。结果12.5～200mg·mL-1的HMF与SH-SY5Y细胞共孵育能明显拮抗叠氮钠的损伤作用,使细胞存活率增高,线粒体跨膜电位升高,并使损伤的微管、微丝结构基本恢复正常,减少Aβ含量。结论HMF能明显拮抗线粒体呼吸链复合体IV缺陷所致的神经细胞损伤,其机制与保护细胞骨架和降低Aβ含量有关,对于防治阿尔采末病等神经退行性疾病有一定应用前景。Aim In order to investigate the effects and mechanisms of hydroxymethyl-furfural （HMF） , an active component extracted from Comus officinalis, on nerve cell damage induced by sodium azide （NaN3） , a specific inhibitor of mitoehondria respiratory chain complex IV. Methods Different concentrations of HMF were incubated with human neuroblastoma cell line SH-SY5Y cells for 24 h,then exposed to 50 mmol · L^-1 sodium azide for 4 h. Cell viability was measured by MTY method and lactic dehydrogenase （LDH） leakage rate. The mitoehondria membrane potential and immunofluorecence-stained cytoskeleton （microtubules and microfilaments） were observed by eonfocal microscopy. The expression of β-amyloid （AL3） was measured by immuno-cytochemistry. Results Pre-incubation of HMF （ 12. 5 -200 mg · L^-1 ） with SH-sY5Y cells an-tagonized the decrease in cell viability and mitochondria membrane potential induced by sodium azide. HMF improved the morphology of neurons, restored the damaged structures of microtubules and microfilaments to normal, and decreased the over-expressions of the intracellular Aβ. Conclusion HMF could protect nerve cells against cell injury induced by mitochondrial deficiency, and its mechanisms might be related to the protection of cytoskeleton and a decrease of intracellular Aβ ,suggesting that HMF might play a potential role in treating Alzheimers disease and other neurodegeneratire diseases.

关 键 词：羟甲基糠醛 山茱萸 线粒体 叠氮钠 SH-SY5Y细胞 膜电位 细胞骨架 Β-淀粉样肽 阿尔采末病 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]