文献类型：期刊文献

中文题名：姜黄素对Aβ_(1-42)诱导的细胞损伤和线粒体途径细胞凋亡的抑制作用

英文题名：Inhibitory effect of curcumin on Aβ_(1-42)-induced cell damage and mitochondrial pathway apoptosis

作者：路书彦[1,2];杨丽[1,2];戴雪伶[1,2];常平[1,2];姜招峰[1,2];黄汉昌[1,2]

第一作者：路书彦

机构：[1]北京联合大学功能食品科学技术研究院;[2]北京联合大学生物活性物质与功能食品北京市重点实验室

第一机构：北京联合大学应用文理学院|北京联合大学生物化学工程学院功能食品科学技术研究院

年份：2017

卷号：31

期号：2

起止页码：138-144

中文期刊名：中国药理学与毒理学杂志

外文期刊名：Chinese Journal of Pharmacology and Toxicology

收录：CSTPCD;;Scopus;北大核心:【北大核心2014】；CSCD:【CSCD2017_2018】；

基金：国家自然科学基金(31471587);北京市教委科技计划面上发展项目(SQKM201411417003)~~

语种：中文

中文关键词：阿尔茨海默病;姜黄素;β-淀粉样蛋白;线粒体膜电位;细胞凋亡

外文关键词：Alzheimer disease; curcumin; β amyloid protein; mitochondrial membrane potential; apoptosis

摘要：目的探讨姜黄素对Aβ_(1-42)诱导的细胞损伤和凋亡的抑制作用。方法采用体外培养的人神经母细胞瘤SH-SY5Y细胞,分为溶剂对照组、Aβ_(1-42)10μmol·L^(-1)损伤组、Aβ_(1-42)10μmol·L^(-1)+姜黄素1,5和10μmol·L^(-1)保护组及姜黄素10μmol·L^(-1)对照组;噻唑蓝(MTT)法测定细胞存活率,酶活性法检测细胞培养液中乳酸脱氢酶(LDH)的含量以考察细胞损伤程度;AnnexinⅤ-FITC/PI染色法测定细胞凋亡;JC-1染色法检测线粒体膜电位变化;比色法测定胱天蛋白酶9和胱天蛋白酶3的活性;Western蛋白印迹法检测胱天蛋白酶3表达。结果与溶剂对照组比,Aβ_(1-42)10μmol·L^(-1)损伤组细胞存活率显著降低(P<0.01)。与Aβ_(1-42)10μmol·L^(-1)损伤组比较,姜黄素5和10μmol·L^(-1)缓解了Aβ_(1-42)诱导的细胞存活率下降(P<0.05),降低了Aβ_(1-42)诱导的乳酸脱氢酶释放水平(P<0.01)和细胞早期及晚期凋亡率(P<0.01)。姜黄素抑制了Aβ_(1-42)诱导的细胞线粒体膜电位去极化作用(P<0.01);姜黄素1~10μmol·L^(-1)抑制了Aβ_(1-42)诱导的胱天蛋白酶9及胱天蛋白酶3级联激活作用,且呈浓度依赖性(r=0.990,P<0.01;r=0.996,P<0.01)。姜黄素10μmol·L^(-1)对照组以上指标与溶剂对照组无明显差异。结论姜黄素可能通过升高线粒体膜电位、降低胱天蛋白酶活性抑制Aβ_(1-42)诱导的细胞损伤和线粒体途径细胞凋亡。
OBJECTIVE To investigate the protective effect of curcumin on Aβ1-42damaged cells.METHODS SH-SY5Y cells were cultured with Aβ1-420 μmol·L^-1in the absence or presence of curcumin1, 5 or 10 μmol·L^-1.Cell viability was assayed by MTT.Cell membrane damage was detected by the concentration of lactate dehydrogenase（LDH） in culture medium.Cell apoptosis was measured by flow cytometry with Annexin Ⅴ-FITC/PI staining.Mitochondrial membrane potential was characterized by fluorescence of JC-1 dye.Enzymatic activity of caspases-9 and-3 was measured by colorimetric assay.Protein expression of caspase-3 was detected by Western blotting.RESULTS Compared with vehicle control, the cell viability, concentration of LDH and both early and late apoptosis in Aβ1-420 μmol·L^-1damaged group were decreased（P〈0.01）.However, the cell viability, release of LDH and both early and late apoptosis in curcumin group were promoted compared with that in Aβ1-420 μmol·L^-1damaged group.Curcumin inhibited Aβ1-42induced depolarization of mitochondrial membrane potential（P〈0.01）,and attenuated Aβ1-42induced activation of both caspases9 and caspases3 in a concentration-dependent manner, respectively（r=0.990, P〈0.01; r=0.996, P〈0.01）.There were no significant differences in the above detected indexes between curcumin 10 μmol·L^-1group and vehicle control group.CONCLUSION Curcumin inhibits Aβ1-42induced cel damage and apoptosis by promoting mitochondrial membrane potential and depressing the activation of caspases.