沉香倍半萜ZH-13保护内质网应激诱导神经元损伤作用机制
Mechanism of Aquilariae Lignum Resinatum sesquiterpene ZH-13 in protecting neuronal injury induced by endoplasmic reticulum stress
高云 1薛伟刚 1王俊娇 1马家乐 1黄杨丽 1赵茂源 1张瑞杰 1郑得丽 1阴紫钰 1赵云芳 2郑姣 2李军1
作者信息
- 1. 北京中医药大学中医药研究院中药现代研究中心,北京 102488;北京中医药大学中药学院,北京 102488
- 2. 北京中医药大学中医药研究院中药现代研究中心,北京 102488
- 折叠
摘要
目的 基于沉香镇静安神的传统功效,探讨其活性成分倍半萜ZH-13对内质网应激诱导神经元损伤的改善作用及作用机制.方法 采用内质网应激诱导剂衣霉素(tunicamycin,Tm)诱导大鼠肾上腺嗜铬细胞瘤PC12细胞内质网应激,检测倍半萜ZH-13对细胞存活率、细胞凋亡及内质网应激相关蛋白表达的影响.结果 Tm以剂量相关性降低PC12细胞的存活率(P＜0.01),ZH-13显著提高Tm损伤PC12细胞的存活率(P＜0.01)并改善内质网应激.通过对蛋白激酶样内质网激酶(protein kinase RNA-like endoplasmic reticulum kinase,PERK)、肌醇需求酶 1(inositol-requiring enzyme 1,IRE1)、转录活化因子6(activating transcription factor 6,ATF6)3条通路相关蛋白的分析,证实ZH-13显著抑制内质网应激PERK通路的过度激活(P＜0.05),而对IRE1、ATF6通路的作用不明显.结论 ZH-13通过调控PERK通路改善内质网应激介导的PC12细胞损伤,显示出良好的神经保护作用.
Abstract
Objective To explore the improvement effect and mechanism of action of the active component sesquiterpene ZH-13 on endoplasmic reticulum(ER)stress-induced neuronal injury based on the traditional sedative effect of Chenxiang(Aquilariae Lignum Resinatum).Methods The ER stress inducer tunicamycin(Tm)was used to trigger ER stress in PC12 cells,and the effects of ZH-13 on cell viability,apoptosis,and expression of ER stress-related proteins were examined.Results The results showed that Tm reduced PC12 cell in a dose-dependent manner(P＜0.01),and ZH-13 significantly increased cell viability(P＜0.01)and ameliorated ER stress.By analyzing the proteins related to protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),and activating transcription factor 6(ATF6),it was confirmed that ZH-13 significantly inhibited the overactivation of the PERK pathway in ER stress(P＜0.05),with no obvious effect on the IRE1 and ATF6 pathways.Conclusion ZH-13 improves ER stress-mediated damage in PC12 cells by regulating the PERK pathway,demonstrating a good neuroprotective effect.
关键词
沉香/倍半萜ZH-13/内质网应激/IRE1通路/ATF6通路/PERK通路Key words
Aquilariae Lignum Resinatum/sesquiterpene ZH-13/endoplasmic reticulum stress/IRE1 pathway/ATF6 pathway/PERK pathway引用本文复制引用
出版年
2025
NETL
NSTL
万方数据