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。

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.

R285.5

国家自然科学基金项目（82074050）;国家中医药管理局青年岐黄学者支持项目[国中医药人教函（2022）256号];北京市自然科学基金项目（7232296）