洛伐他汀对抗人神经母细胞瘤SH-SY5Y细胞β-淀粉样蛋白的非胆固醇依赖性保护作用Protective Effect of Lovastatin on SH-SY5Y Cells against β-amyloid Peptide in Non Cholesterol Dependence Way
赵亮,官志忠
ZHAO Liang,GUAN Zhizhong
摘要(Abstract):
目的:观察洛伐他汀对过表达APP670/671的人神经母细胞瘤SH-SY5Y细胞活性及β-淀粉样蛋白(Aβ)二聚体合成的影响。方法:转染并鉴定过表达APP670/671的SH-SY5Y细胞,筛选无细胞毒性、不影响细胞胆固醇水平浓度的洛伐他汀处理SH-SY5Y细胞24 h,采用CCK-8试验检测细胞的存活率,蛋白印迹法检测Aβ二聚体的蛋白表达水平。结果:过表达APP670/671的SH-SY5Y细胞中APP的蛋白及mRNA表达水平均明显高于野生型细胞;用0.1μmol/L的洛伐他汀处理SH-SY5Y细胞,未见明显细胞毒性作用,胆固醇水平亦未见明显改变;0.1μmol/L洛伐他汀预处理SH-SY5Y细胞24 h,能提高细胞存活率,减少Aβ二聚体的分泌。结论:洛伐他汀具有神经保护作用,可能与减少毒性Aβ的合成有关。
Objective:To observe the effect of lovastatin on APP670/671 gene over-expressed human neuroblastoma SH-SY5 Y cell activity and the synthesis of dimer of beta amyloid protein(Aβ).Methods:The human APP670/671 gene was transfected into the SH-SY5 Y cells and identified.The best concentration of lovastatin which had no cell toxicity and did not affect the cell cholesterol concentration was screened,which treated SH-SY5 Y cells for 24 h.Then,CCK-8 test was used to detect the cell survival rate,and Western blot was adopted to detect the protein expression level of Aβ dimer.Results:The protein and mRNA levels of APP in SH-SY5 Y/APPSWE cells were obviously higher than the SH-SY5 Y wild type cells.No toxic effect and no changes in cholestetol level were observed in the cells treated with 0.1 μmol/L lovastatin for 24 h.0.1 μmol/l lovastatin pretreatment of SH-SY5 Y cells with 24 h could improve the survival rate of cells and decreased Aβ dimer secretion.Conclusions:Lovastatin has a neuroprotective effect,which may be related to reducing the toxic Aβdimer synthesis.
关键词(KeyWords):
洛伐他汀;β-淀粉样蛋白;淀粉样前体蛋白;阿尔兹海默病
lovastatin;β-amyloid protein;amyloid precursor protein;Alzheimer's disease
基金项目(Foundation): 国家自然科学基金(81260173);; 教育部“长江学者和创新团队发展计划资助”(IRT13058);; 贵州省科技计划[黔科合重大专项字(2014)6008号];; 贵州省创新计划项目[黔教合协同创新中心(2014)06]
作者(Author):
赵亮,官志忠
ZHAO Liang,GUAN Zhizhong
DOI: 10.19367/j.cnki.1000-2707.2016.12.002
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