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芥子酸对Aβ42诱导PC12细胞损伤的改善作用及机制 Δ

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薛 迪 ，刘学伟 ，汪 娜 ，刘宇超 ，徐 涛 ，裴芳艺（1.齐齐哈尔医学院药学院，黑龙江 齐齐哈尔 161006；
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2.齐齐哈尔医学院精神卫生学院，黑龙江 齐齐哈尔 161006；3.齐齐哈尔医学院基础医学院，黑龙江 齐齐哈尔
161006；4.齐齐哈尔医学院科研处，黑龙江 齐齐哈尔 161006）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）05-0597-06
DOI 10.6039/j.issn.1001-0408.2022.05.15

摘 要 目的 研究芥子酸对β-淀粉样蛋白42（Aβ 42 ）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10 μmol/L）培养1 h；然后除对照组外，其余4组分别加入2 μmol/L Aβ 42处理24 h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100 μmol/L 芥子酸，继续培养 24 h。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CREB mRNA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Aβ 42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
CREB mRNA转录、激活cAMP/PKA/CREB信号通路有关。
关键词 芥子酸；cAMP/PKA/CREB信号通路；阿尔茨海默病；β-淀粉样蛋白

Improvement effects of sinapic acid on Aβ42-induced injury of PC12 cells and the mechanism
XUE Di ，LIU Xuewei ，WANG Na ，LIU Yuchao ，XU Tao ，PEI Fangyi（1. School of Pharmacy，Qiqihar
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Medical University， Heilongjiang Qiqihar 161006， China； 2. School of Mental Health，Qiqihar Medical
University，Heilongjiang Qiqihar 161006，China；3. School of Basic Medicine，Qiqihar Medical University，
Heilongjiang Qiqihar 161006， China； 4. Office of Academic Research， Qiqihar Medical University，
Heilongjiang Qiqihar 161006，China）
ABSTRACT OBJECTIVE To study the improvement effects of sinapic acid on A β 42-induced injury of PC12 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 LY294002 and U0126（10 μmol/L）for 1 h；except for control group，other four groups were treated with 2 μmol/L Aβ 42 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 PC12 cells was detected and the
morphology of PC12 cells was observed. The content of A β 42，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 PC12 cells，mRNA
expression of CREB and protein expressions of cAMP，PKA and p-CREB were increased significantly （P＜0.05），while the
content of Aβ 42 was decreased significantly（P＜0.05）；cell morphology was significantly improved and synapses increased. After
intervened with PI3K and ERK inhibitors，the survival rate of PC12 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
Δ 基金项目：黑龙江省省属高等学校基本科研业务费科研项目 survival rate of PC12 cells injured by A β 42，improve cell
（No.2021-KYYWF-0349）
morphology and decrease the content of Aβ 42，the mechanism
＊助理研究员，硕士。研究方向：天然药物防治神经退行性疾病
of which may be associated with promoting the gene
的活性成分筛选及作用机制。电话：0452-2663615。E-mail：282832817
transcription of CREB， and activating cAMP/PKA/CREB
@qq.com
# 通信作者：工程师。研究方向：天然药物防治神经退行性疾病的 signaling pathway.
活性成分筛选及作用机制。电话：0452-2663875。E-mail：liuyuchao1989 KEYWORDS sinapic acid；cAMP/PKA/CREB signaling
@126.com pathway；Alzheimer’s disease；β-amyloid protein

中国药房 2022年第33卷第5期 China Pharmacy 2022 Vol. 33 No. 5 ·597 ·