Li Shuai, Zhao Jingyuan, Xi Yan, Ren Jiaqi, Zhu Yanna, Lu Yan, Dong Deshi
Department of Pharmacy, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
Neural Regen Res. 2023 Nov;18(11):2424-2428. doi: 10.4103/1673-5374.371366.
Dl-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke. However, the precise underlying mechanism requires further investigation. In this study, we investigated the molecular mechanism of Dl-3-n-butylphthalide action by various means. We used hydrogen peroxide to induce injury to PC12 cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of Dl-3-n-butylphthalide. We found that Dl-3-n-butylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis. Furthermore, Dl-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3. Dl-3-n-butylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α, the key transcription factor that regulates Bax and Bnip3 genes. These findings suggest that Dl-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.
丁苯酞用于治疗轻度和中度急性缺血性脑卒中。然而，其确切的潜在机制仍需进一步研究。在本研究中，我们通过多种方法探究了丁苯酞作用的分子机制。我们用过氧化氢诱导PC12细胞和RAW264.7细胞损伤，以模拟体外脑卒中时的神经元氧化应激损伤，并检测丁苯酞的作用效果。我们发现，丁苯酞预处理显著抑制了过氧化氢所致PC12细胞活力降低和活性氧生成，并抑制细胞凋亡。此外，丁苯酞预处理抑制了促凋亡基因Bax和Bnip3的表达。丁苯酞还促进了缺氧诱导因子1α的泛素化和降解，缺氧诱导因子1α是调控Bax和Bnip3基因的关键转录因子。这些研究结果表明，丁苯酞通过促进缺氧诱导因子-1α泛素化和降解以及抑制细胞凋亡，对脑卒中发挥神经保护作用。
