三七皂苷R1对Aβ1—42诱导的SH—SY5Y细胞凋亡的保护作用(1)
[摘要]目的：探讨三七皂苷R1对Aβ1-42诱导SH-SY5Y细胞凋亡的保护机制。方法：MTT法检测细胞存活率;PI/AnnexinV双染流式细胞术分析细胞凋亡率;Westernblot法检测细胞中Bax，Bcl-2的表达;ELISA法检测caspase-3，caspase-8及caspase-9的酶活性。结果：6.25，12.5，25，50，100nmol·L-1的三七皂苷R1对Aβ1-42诱导的SH-SY5Y细胞凋亡均有一定保护作用，并呈剂量依赖关系;PI/AnnexinV双染流式细胞术检测结果表明Aβ1-42可诱导SH-SY5Y细胞发生凋亡，6.25～100nmol·L-1的三七皂苷R1可显著降低细胞凋亡率。Westernblot结果显示，6.25～100nmol·L-1的三七皂苷R1可下调Bax表达，上调Bcl-2表达;ELISA分析显示不同剂量的三七皂苷R1可抑制Aβ1-42诱导的SH-SY5Y细胞caspase-3和caspase-9的激活，但对caspase-8的激活没有影响。结论：三七皂苷R1通过抑制线粒体相关的凋亡通路激活，减少Aβ1-42诱导的SH-SY5Y细胞凋亡。
, 百拇医药
[关键词]阿尔茨海默病;三七皂苷R1;细胞凋亡;线粒体;SH-SY5Y细胞;Aβ1-42
Protective effects of notoginsenoside R1 against amyloid-β(1-42)
induced mitochondrial apopototic death in SH-SY5Y cells
MA Tao1，2， XIN Wen-feng1，3，4， ZHANG Wen-sheng1，3，4*， WANG Yong-yan5
(1.Beijing Normal University， Beijing Key Laboratory for Protection and Utilization of Chinese Medicine Resources， Beijing 100875， China;
, 百拇医药
2. Dongfang Hospital affiliated to Beijing University of Chinese Medicine， Beijing 100078， China;
3. Beijing Normal University， Engineering Research Center of Natural Medicine， the Ministry of Education of China， Beijing 100875， China;
4. Yun Nan Sanqi Biotechnology and Pharmaceutical Engineering Center， Kunming 652200， China;
5. China Academy of Chinese Medical Sciences， Beijing 100700， China)
, http://www.100md.com
[Abstract]Objective： To investigate the effects and underlying mechanism of notoginsenoside R1 on amyloid-β(1-42) (Aβ1-42) induced mitochondrial apoptotic death in SH-SY5Y cells. Method： Cell viability was assayed by MTT， apoptotic rates were analyzed with PI/Annexin V flow cytometry， Bax and Bcl-2 expression were detected with Western blotting， enzymatic activity of caspase-3， caspase-8 and caspase-9 were measured by ELISA assay. Result： The 6.25-100 nmol·L-1 of notoginsenoside R1 attenuate Aβ1-42 induced apoptotic death of SH-SY5Y in dose dependent manner. The ratio of Bcl-2/Bax was elevated in SH-SY5Y with notoginsenoside R1 treatment. Caspase-3 and caspase-9 were activated with notoginsenoside R1 treatment while caspase-8 was not affected. Conclusion： Notoginsenoside R1 could protect SH-SY5Y cells from Aβ1-42 induced apoptosis via mitochondria related apoptotic pathway.
, 百拇医药
[Key words]Alzheimer′s disease; notoginsenoside R1; cell apoptosis; mitochondria; SH-SY5Y; Aβ1-42
doi：10.4268/cjcmm20150226
阿尔茨海默病(Alzheimer′sdisease，AD)，是一种以认知障碍为主要表现的中枢神经系统退行性病变。随着全球人口老龄化，AD患病率逐年增加[1]。AD发病机制复杂，其病因迄今还不明确。其中β淀粉样蛋白(Aβ)在脑内过度累积形成的淀粉样蛋白斑块是AD的典型病理特征。Aβ蛋白具有多种毒性作用，可引起线粒体应激、氧化应激、钙离子失调、膜结构损伤等，导致神经细胞凋亡，神经突触脱失，认知记忆能力受损[2]。以Aβ毒性蛋白为靶标，开展研究具有重要意义。Aβ蛋白有40和42个氨基酸长度2种主要形式，其中Aβ1-42易于寡聚化，更具毒性，是AD患者脑中Aβ蛋白的主要形式[3]。目前上市的AD临床治疗药物，主要以乙酰胆碱酯酶抑制剂(AChEI)和N-甲酰-D-天门冬氨酸(NMDA)受体拮抗剂为主，对AD患者症状具有一定改善作用，但仅针对AD病理过程的某一环节发挥作用，局限性较大。因此，研究开发新的抗AD药物具有重要意义[4-7]。, 百拇医药(马涛 辛文锋 张文生 王永炎)
, 百拇医药
[关键词]阿尔茨海默病;三七皂苷R1;细胞凋亡;线粒体;SH-SY5Y细胞;Aβ1-42
Protective effects of notoginsenoside R1 against amyloid-β(1-42)
induced mitochondrial apopototic death in SH-SY5Y cells
MA Tao1，2， XIN Wen-feng1，3，4， ZHANG Wen-sheng1，3，4*， WANG Yong-yan5
(1.Beijing Normal University， Beijing Key Laboratory for Protection and Utilization of Chinese Medicine Resources， Beijing 100875， China;
, 百拇医药
2. Dongfang Hospital affiliated to Beijing University of Chinese Medicine， Beijing 100078， China;
3. Beijing Normal University， Engineering Research Center of Natural Medicine， the Ministry of Education of China， Beijing 100875， China;
4. Yun Nan Sanqi Biotechnology and Pharmaceutical Engineering Center， Kunming 652200， China;
5. China Academy of Chinese Medical Sciences， Beijing 100700， China)
, http://www.100md.com
[Abstract]Objective： To investigate the effects and underlying mechanism of notoginsenoside R1 on amyloid-β(1-42) (Aβ1-42) induced mitochondrial apoptotic death in SH-SY5Y cells. Method： Cell viability was assayed by MTT， apoptotic rates were analyzed with PI/Annexin V flow cytometry， Bax and Bcl-2 expression were detected with Western blotting， enzymatic activity of caspase-3， caspase-8 and caspase-9 were measured by ELISA assay. Result： The 6.25-100 nmol·L-1 of notoginsenoside R1 attenuate Aβ1-42 induced apoptotic death of SH-SY5Y in dose dependent manner. The ratio of Bcl-2/Bax was elevated in SH-SY5Y with notoginsenoside R1 treatment. Caspase-3 and caspase-9 were activated with notoginsenoside R1 treatment while caspase-8 was not affected. Conclusion： Notoginsenoside R1 could protect SH-SY5Y cells from Aβ1-42 induced apoptosis via mitochondria related apoptotic pathway.
, 百拇医药
[Key words]Alzheimer′s disease; notoginsenoside R1; cell apoptosis; mitochondria; SH-SY5Y; Aβ1-42
doi：10.4268/cjcmm20150226
阿尔茨海默病(Alzheimer′sdisease，AD)，是一种以认知障碍为主要表现的中枢神经系统退行性病变。随着全球人口老龄化，AD患病率逐年增加[1]。AD发病机制复杂，其病因迄今还不明确。其中β淀粉样蛋白(Aβ)在脑内过度累积形成的淀粉样蛋白斑块是AD的典型病理特征。Aβ蛋白具有多种毒性作用，可引起线粒体应激、氧化应激、钙离子失调、膜结构损伤等，导致神经细胞凋亡，神经突触脱失，认知记忆能力受损[2]。以Aβ毒性蛋白为靶标，开展研究具有重要意义。Aβ蛋白有40和42个氨基酸长度2种主要形式，其中Aβ1-42易于寡聚化，更具毒性，是AD患者脑中Aβ蛋白的主要形式[3]。目前上市的AD临床治疗药物，主要以乙酰胆碱酯酶抑制剂(AChEI)和N-甲酰-D-天门冬氨酸(NMDA)受体拮抗剂为主，对AD患者症状具有一定改善作用，但仅针对AD病理过程的某一环节发挥作用，局限性较大。因此，研究开发新的抗AD药物具有重要意义[4-7]。, 百拇医药(马涛 辛文锋 张文生 王永炎)