邵梅,陈生弟,刘振国

• 1:上海第二医科大学瑞金医院神经科
• 2:上海第二医科大学瑞金医院神经科
• 3:上海第二医科大学瑞金医院神经科 上海200025
• 4:上海200025

摘要(Abstract)：

目的　探讨β-淀粉样蛋白 ( Aβ)在形成淀粉样沉积前对体外培养的 PC1 2细胞的毒性作用。方法　应用流式细胞仪检测 Aβ的剂量依赖性毒性 ;应用 DNA琼脂糖凝胶电泳、DNA末端标记和电镜判断 Aβ损伤细胞的途径。结果　流式细胞仪检测发现随着 Aβ2 5 -35浓度的增加 ,PC1 2细胞的死亡率增加 ;加入 1 0 μmol/L Aβ2 5 -35 2 4 h后 ,经 TUNEL发现细胞核着色 ,并可见细胞核碎片 ;DNA琼脂糖凝胶电泳可见间隔 1 80～ 2 0 0 bp左右的梯度条带 ;电镜显示细胞核浓缩 ,胞浆内有空泡形成 ,胞浆内细胞器完好。结论　 Aβ在形成纤维状沉积前即对神经细胞有毒性作用 ,可促进神经细胞的凋亡。

关键词(KeyWords)： 可溶性淀粉样蛋白25-35片段;大鼠嗜铬细胞瘤细胞;凋亡;阿尔茨海默病

Abstract:

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基金项目(Foundation): 上海市科委自然科学基金面上资助项目 ( 99ZB14 0 19)

作者(Author): 邵梅,陈生弟,刘振国

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参考文献(References)：

• [1]AndersonA,SuJ,CotmanCW.DNA damage andapoptosis inAlzheimer's disease:colocalization withc-jun immunoactivity,relationship to brain area,andeffectof postmortemdelay[J].JNeurosci,1996,16:1710-1719.
• [2]SuJ,AndersonA.CummingsB,et al.Immunohis-tochemical evidence for apoptosis inAlzheimer's dis-ease[J].Neuroreport,1995,5:2529-2533.
• [3]PikeCJ,BurdickD,WalencewiczAJ,etal.Neurode-generation induced by amyloid peptides in vitro:therole ofβ peptide assembly state[J].J Neurosci,1993,13:1676-1687.
• [4]YankerBA,DuffyLK,KirschnerDA.Neurotrophicand neurotoxic effects of amyloidβ protein:reversalby tachykinin neuroprptide[J].Science,1990,250:279-282.
• [5]RajindeB,LinH,LalR.Fresh and global amyloidβprotein(1-42) induces rapid cellular degeneration:evidence forAβP channel-mediated cellular toxicityA[J].FASEB J,2000,14:1233-1243.
• [6]KnopsJ,Johnson-WoodK,SchenkDB,et al.Isola-tion of baculovirus secreted and full-lengthβ-amyloidprecursor protein[J].JBiolChem,1991,266:7285-7290.
• [7]ScheunerD,EckmanC,JensenM,et al.Secretedamyloid beta-protein similar to that in the senileplaques ofAlzheimer's diseaseis increased in vivo bythe presenilin1 and2 andAPP mutations linked tofamilialAlzheimer's disease[J].NatMed,1996,2:864-870
• [8]SuzukiN,CheungTT,CaiXD,et al.An increasedpercentage of long amyloid beta protein secreted byfamilial amyloid beta protein precursor( betaAPP717) mutants[J].Science,1994,264:1336-1340.
• [9]SelkoeDJ.Alzheimer's disease:a central role foramyloid[J].JNeuropathExpNeurol,1994,53:438-447.
• [10]SelkoeDJ.Alzheimer's disease:genotypes,pheno-types and treatment[J].Science,1997,275:630-631.
• [11]YankerBA.Mechanism of neurodegeneration inAlzheimer's disease[J].Neuron,1996,16:921-932.
• [12]LooD,CopaniA,PikeCJ,etal.Apoptosis is inducedbyβ-amyloid in cultured central nervous neurons[J].ProcNatlAcadSciUSA,1993,90:7951-7955.
• [13]YangF,SunX,BeechW,etal.Antibody to caspase-cleaved action detects apoptosis in differentiated neu-roblastoma and plaque-associated neurons and mi-croglia inAlzheimer's disease[J].AmJ Pathol,1998,152:379-389.
• [14]BehlC,DavisJ,KlierFG,etal.Amyloid beta peptideinduces necrosisratherthan apoptosis[J].BrainRes,1994,645:253-264.