目的 基于沉香鎮(zhèn)靜安神的傳統(tǒng)功效，探討其活性成分倍半萜ZH-13對(duì)內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)神經(jīng)元損傷的改善作用及作用機(jī)制。方法 采用內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)劑衣霉素（tunicamycin，Tm）誘導(dǎo)大鼠腎上腺嗜鉻細(xì)胞瘤PC12細(xì)胞內(nèi)質(zhì)網(wǎng)應(yīng)激，檢測(cè)倍半萜ZH-13對(duì)細(xì)胞存活率、細(xì)胞凋亡及內(nèi)質(zhì)網(wǎng)應(yīng)激相關(guān)蛋白表達(dá)的影響。結(jié)果 Tm以劑量相關(guān)性降低PC12細(xì)胞的存活率（P＜0.01），ZH-13顯著提高Tm損傷PC12細(xì)胞的存活率（P＜0.01）并改善內(nèi)質(zhì)網(wǎng)應(yīng)激。通過對(duì)蛋白激酶樣內(nèi)質(zhì)網(wǎng)激酶（protein kinase RNA-like endoplasmic reticulum kinase，PERK）、肌醇需求酶1（inositol-requiring enzyme 1，IRE1）、轉(zhuǎn)錄活化因子6（activating transcription factor 6，ATF6）3條通路相關(guān)蛋白的分析，證實(shí)ZH-13顯著抑制內(nèi)質(zhì)網(wǎng)應(yīng)激PERK通路的過度激活（P＜0.05），而對(duì)IRE1、ATF6通路的作用不明顯。結(jié)論 ZH-13通過調(diào)控PERK通路改善內(nèi)質(zhì)網(wǎng)應(yīng)激介導(dǎo)的PC12細(xì)胞損傷，顯示出良好的神經(jīng)保護(hù)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

國家自然科學(xué)基金項(xiàng)目（82074050）;國家中醫(yī)藥管理局青年岐黃學(xué)者支持項(xiàng)目[國中醫(yī)藥人教函（2022）256號(hào)];北京市自然科學(xué)基金項(xiàng)目（7232296）