芥子酸对Aβ42诱导PC12细胞损伤的改善作用及机制 点击下载
论文标题: 芥子酸对Aβ42诱导PC12细胞损伤的改善作用及机制
英文标题:
中文摘要: 目的 研究芥子酸对β-淀粉样蛋白42(Aβ42)诱导PC12细胞损伤的改善作用及机制。方法将PC12细胞分为对照组、模型组、芥子酸组、激活磷脂酰肌醇-3-激酶(PI3K)抑制剂组、细胞外信号调节蛋白激酶(ERK)抑制剂组,各抑制剂组先分别加入LY294002和U0126(均为10μmol/L)培养1h;然后除对照组外,其余4组分别加入2μmol/LAβ42处理24h以复制阿尔茨海默病细胞模型;除对照组及模型组外,其余3组再分别加入100μmol/L芥子酸,继续培养24h。检测细胞存活率并观察其形态,检测细胞中Aβ42含量、cAMP反应元件结合蛋白(CREB)mRNA表达水平以及环磷酸腺苷(cAMP)、蛋白激酶A(PKA)、CREB、磷酸化CREB(p-CREB)蛋白表达水平。结果经芥子酸作用后,PC12细胞存活率、细胞中CREBmRNA表达水平以及cAMP、PKA、p-CREB蛋白表达水平均显著升高(P<0.05),细胞中Aβ42含量显著降低(P<0.05),细胞形态明显改善、突触增多;而经PI3K、ERK抑制剂干预后,PC12细胞存活率及上述mRNA和蛋白表达水平均被显著逆转(P<0.05或P<0.01),细胞形态不规则、碎片增多,且突触连接减少。结论芥子酸可升高Aβ42诱导损伤的PC12细胞存活率,改善细胞形态,降低细胞中Aβ42含量,其作用机制可能与促进细胞中CREBmRNA转录、激活cAMP/PKA/CREB信号通路有关。
英文摘要: OBJECTIVE To s tudy the improvement effects of sinapic acid on Aβ42-induced injury of PC 12 cells and the mechanism. METHODS PC12 cells were divided into five groups :control group ,model group ,sinapic acid group ,phosphoinositide- 3-kinase(PI3K)inhibitor group and extracellular signal-regulated kinase (ERK)inhibitor group. Each inhibitor group was added with LY 294002 and U 0126(10 μmol/L)for 1 h;except for control group ,other four groups were treated with 2 μmol/L Aβ42 for 24 h to replicate the Alzheimer ’s disease cell model ;except for control group and model group ,other three groups were added with 100 μmol/L sinapic acid respectively. After 24 hours of continuous culture ,survival rate of PC 12 cells was detected and the morphology of PC 12 cells was observed. The content of Aβ42,mRNA expression of cAMP response element binding protein (CREB),protein expression of cyclic adenosine monophosphate (cAMP),protein kinase A (PKA),CREB signaling pathway and phosphorylated CREB (p-CREB)were detected. RESULTS After treated with sinapic acid ,the survival rate of PC 12 cells,mRNA expression of CREB and protein expressions of cAMP ,PKA and p-CREB were increased significantly (P<0.05),while the content of Aβ42 was decreased significantly (P<0.05);cell morphology was significantly improved and synapses increased. After intervened with PI 3K and ERK inhibitors ,the survival rate of PC 12 cells,above mRNA and protein expressions were reversed significantly (P<0.05 or P<0.01);cell morphology was irregular ,the fragments increased ,and the synaptic connections decreased. CONCLUSIONS Sinapic acid can improve the survival rate of PC 12 cells injured by A β 42,improve cell (No.2021-KYYWF-0349) morphology and decrease the content of Aβ42,the mechanism of which may be associated with promoting the gene transcription of CREB , and activating cAMP/PKA/CREB signaling pathway.
期刊: 2022年第33卷第05期
作者: 薛迪,刘学伟,汪娜,刘宇超,徐涛,裴芳艺
英文作者: XUE Di,LIU Xuewei ,WANG Na,LIU Yuchao ,XU Tao,PEI Fangyi
关键字: 芥子酸;cAMP/PKA/CREB信号通路;阿尔茨海默病;β-淀粉样蛋白
KEYWORDS: sinapic acid ;cAMP/PKA/CREB signaling
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