β-淀粉样肽诱导单核细胞培养上清液致神经细胞损伤模型的建立  

Development of Cell Model of β Amyloid-Induced Monocyte Supernatant to Damage Neural Cells

作　　者：李玮[1] 李林[1] 褚燕琦[1] 李雅莉[1] 索爱琴[2] 张健[2] 

机构地区：[1]首都医科大学宣武医院药物研究室教育部神经变性病学重点实验室,北京100053 [2]河南省人民医院神经内科,河南郑州450003

出　　处：《中国神经免疫学和神经病学杂志》2007年第3期121-123,126,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家重点基础研究"973"计划基金资助项目(2003CB517104);国家自然科学基金资助项目(30472184);北京市自然科学基金资助项目(7032013;7050001)

摘　　要：目的建立β淀粉样肽（Aβ1-40）诱导THP-1单核细胞（模拟小胶质细胞）的上清液致SK—N—SH神经细胞损伤的细胞模型，并研究神经细胞损伤的机制。方法用乳酸脱氢酶（LDH）漏出率观察人神经母细胞瘤SK-N—SH细胞系的损伤程度；以放射免疫法测定THP-1单核细胞培养的上清液中炎性细胞因子IL-1β、IL-8和肿瘤坏死因子-α（TNF-α）浓度。结果Aβ1-40（终浓度125nmol／L）与THP-1单核细胞孵育0．5～4h，取上清液加入到培养的SK-N—SH神经细胞共孵育24h，SK-N-SH神经细胞LDH漏出率较对照组明显增高，其中Aβ诱导THP-1细胞2h的上清液对SK—N—SH神经细胞的损伤最明显。Aβ1-40与THP-1单核细胞孵育2h，其上清液中炎性细胞因子IL-1β、IL-8和TNF-α水平比对照组明显增高。结论Aβ1-40诱导THP-1单核细胞可作为免疫炎性损伤的细胞模型，炎性细胞因子水平增高是Aβ引起神经细胞损伤的机制。Objective To establish the cell model of neuroblastoma SK-N-SH cell line impaired by supernatant of THP-1 monocytes which was induced by β amyloid （Aβ1-40）, and to investigate the mechanism of neural cell damage. Methods The impairment of SK-N-SH neural cells was measured by lactate dehydrogenase （LDH） leakage rate. The concentrations of inflammatory cytokines IL-β, IL-8 and tumor necrosis factor-α （TNF-α） in supernatant of THP-1 monocytes were determined by radioimmunoassay. Results Aβ1-40 （final concentration 125 nmol/L） was incubated with THP-1 monocytes for 0. 5-4 h, then the supernatant was added to cultured SK-N- SH neural cells and incubated for 24h;the LDH leakage rate was significantly increased, and the SK-N-SH neural cells were damaged severely by the supernatant of THP-1 monocytes incubated with Aβ1-40 for 2 h. The levels of inflammatory cytokines IL-1β, IL-8 and TNF-α were significantly increased in the supernatant of THP-1 monocytes incubated with 125 nmol/L Aβ1-40 for 2 h, compared with the control group. Conclusions Aβ1-40- induced THP-1 monocytes can be served as a cell model of inflammatory injury; the increase of inflammatory cytokines may be the mechanism of Aβ impairing neural cells.

关 键 词：Β淀粉样肽 炎性细胞因子 单核细胞系 阿尔茨海默病 细胞模型 

分 类 号：R741.02[医药卫生—神经病学与精神病学]