[關鍵詞]
[摘要]
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對內(nèi)質(zhì)網(wǎng)應激誘導神經(jīng)元損傷的改善作用及作用機制。方法 采用內(nèi)質(zhì)網(wǎng)應激誘導劑衣霉素(tunicamycin,Tm)誘導大鼠腎上腺嗜鉻細胞瘤PC12細胞內(nèi)質(zhì)網(wǎng)應激,檢測倍半萜ZH-13對細胞存活率、細胞凋亡及內(nèi)質(zhì)網(wǎng)應激相關蛋白表達的影響。結(jié)果 Tm以劑量相關性降低PC12細胞的存活率(P<0.01),ZH-13顯著提高Tm損傷PC12細胞的存活率(P<0.01)并改善內(nèi)質(zhì)網(wǎng)應激。通過對蛋白激酶樣內(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條通路相關蛋白的分析,證實ZH-13顯著抑制內(nèi)質(zhì)網(wǎng)應激PERK通路的過度激活(P<0.05),而對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)應激介導的PC12細胞損傷,顯示出良好的神經(jīng)保護作用。
[Key word]
[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.
[中圖分類號]
R285.5
[基金項目]
國家自然科學基金項目(82074050);國家中醫(yī)藥管理局青年岐黃學者支持項目[國中醫(yī)藥人教函(2022)256號];北京市自然科學基金項目(7232296)