薛迪 刘宇超 汪娜 刘学伟

中圖分类号 R285;R741 文献标志码 A 文章编号 1001-0408（2021）10-1181-06

DOI 10.6039/j.issn.1001-0408.2021.10.05

摘 要 目的：研究芥子酸对β-淀粉样蛋白1-42（Aβ1-42）诱导的大鼠肾上腺髓质嗜铬细胞瘤细胞（PC12细胞）损伤的改善作用，并探讨其对脑源性神经营养因子（BDNF）/酪氨酸激酶B（TrkB）/细胞外信号调节激酶（ERK）信号通路的影响。方法：将PC12细胞分为空白组、模型组和芥子酸低、高剂量组（50、100 μmol/L）。除空白组外，其余各组均用2 μmol/L的Aβ1-42诱导细胞损伤;建模24 h后，药物组加入相应药液，培养24 h。观察各组细胞形态变化，检测细胞存活率和细胞中BDNF mRNA的表达情况及其蛋白水平，以及TrkB、ERK1/2、磷酸化ERK1/2（p-ERK1/2）蛋白的表达情况，并计算p-ERK1/2与ERK1/2的比值（p-ERK/ERK比值）。结果：与空白组比较，模型组细胞突触变短，细胞连接较松，贴壁性差，胞质较暗淡，胞浆中有较多颗粒，细胞存活率以及细胞中BDNF mRNA的相对表达量及其蛋白水平，TrkB、p-ERK1/2蛋白的相对表达量和p-ERK/ERK比值均显著降低（P<0.05或P<0.01）。与模型组比较，芥子酸高剂量组细胞病理变化明显改善，细胞存活率以及细胞中BDNF mRNA的相对表达量及其蛋白水平，TrkB、p-ERK蛋白的相对表达量和p-ERK/ERK比值均显著升高（P<0.05或P<0.01）。结论：芥子酸可改善Aβ1-42诱导的PC12细胞损伤，其作用机制可能与激活BDNF/TrkB/ERK信号通路有关。

关键词 芥子酸;阿尔茨海默症;β-淀粉样蛋白1-42;脑源性神经生长因子;酪氨酸激酶B;细胞外信号调节激酶

Effects of Sinapic Acid on Improving PC12 Cell Damage Induced by Aβ1-42 and BDNF/TrkB/ERK Signaling Pathway

XUE Di1，LIU Yuchao2，WANG Na3，LIU Xuewei4（1. School of Pharmacy，Qiqihar Medical University， Heilongjiang Qiqihar 161006， China; 2. Office of Academic Research， Qiqihar Medical University，Heilongjiang Qiqihar 161006，China; 3. School of Basic Medicine，Qiqihar Medical University，Heilongjiang Qiqihar 161006，China; 4. School of Mental Health，Qiqihar Medical University，Heilongjiang Qiqihar 161006，China）

ABSTRACT   OBJECTIVE：To study the improvement effects of sinapic acid （SA） on PC12 cell damage induced by Aβ1-42， and to investigate its effect on brain-derived neurotrophic factor （BDNF） /tyrosine kinase B （TrkB） /extracellular signal-regulated kinase （ERK） signaling pathway. METHODS： PC12 cells were divided into blank group，model group， SA low-dose and high-dose groups （50， 100 μmol/L）. Except for blank group， cell damage was induced by Aβ1-42 in other groups; 24 h after modeling，administration groups were added with the corresponding solution and cultured for 24 h. Morphological changes of cells in each group were observed. Cell survival rate， mRNA expression and protein level of BDNF，protein expression of TrkB，ERK1/2 and phosphorylated ERK1/2 （p-ERK1/2） were detected. p-ERK/ERK ratio was calculated. RESULTS：Compared with blank group，the model group had shorter synapses，looser intercellular junctions，poor adhesion，dim cytoplasm and more granules in cytoplasm. Cell survival rate and mRNA expression and protein level of BDNF， the relative expression of TrkB and p-ERK1/2 protein， p-ERK/ERK ratio were significantly decreased （P<0.05 or P<0.01）. Compared with model group，in SA high-dose group the pathological changes of the cells were significantly improved，the survival rate of the cells，the mRNA expression and protein level of BDNF，the relative expression of TrkB and p-ERK1/2 protein， p-ERK/ERK ratio were significantly increased （P<0.05 or P<0.01）. CONCLUSIONS：SA can improve PC12 cells damage induced by Aβ1-42， the mechanism of which may be associated with activating BDNF/TrkB/ERK signaling pathway.

KEYWORDS   Sinapic acid; Alzheimers disease; Aβ1-42; Brain-derived neurotrophic factor; Tyrosine kinase B; Extracellular signal-regulated kinase

阿尔茨海默病（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[1]。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[2]。Aβ主要包括Aβ1-40和Aβ1-42两种亚型，其中Aβ1-42在AD患者脑内最具神经元毒性，易引起老年斑的形成[2-3]。

目前，美国FDA批准用于治疗AD的药物有两类，一类是胆碱酯酶抑制剂，如多奈哌齐、加兰他敏等;另一类是N-甲基-D-天冬氨酸（NMDA）受体拮抗药，如盐酸美金刚;但这两类药物均不能有效逆转AD的进程[4]。2019年11月，国家药品监督管……