| 摘要: |
| 为研究天然化合物异鼠李素(Isorhamnetin，ISO)对神经元细胞毒性的影响及氧化损伤的保护作用，本研究通过利用6-羟基多巴胺(6-hydroxydopamine，6-OHDA)刺激神经元细胞(SH-SY5Y)系建立细胞氧化损伤模型，分析了ISO对6-OHDA诱导的神经元细胞活性、细胞凋亡相关凋亡蛋白、氧化损伤等相关指标。结果表明:1)6-OHDA(300 μmol/L)能明显降低神经元细胞活性(P<0.01)、诱导细胞凋亡及促凋亡蛋白(Caspase-3、Bax)的表达并降低抗凋亡蛋白Bcl-2的表达，而经ISO处理后能有效抑制6-OHDA导致的神经元细胞损伤。2)6-OHDA可显著诱导细胞中活性氧(Reactive oxygen species，ROS)的产生(P<0.01)、引起谷胱甘肽(GSH)的消耗(P<0.05)并促使线粒体功能紊乱，而经ISO处理后可有效改善6-OHDA致使的氧化损伤和线粒体功能紊乱(P<0.05)。3)ISO不仅能通过上调Keap1/Nrf2信号通路显著提高抗氧化蛋白(GCLC、GCLM、HO-1和NQO1)的表达(P<0.05)，还能显著恢复6-OHDA所降低抗氧化蛋白的表达(P<0.05)。综上，本研究明确了ISO可能通过上调Keap1/Nrf2信号通路抑制6-OHDA诱导的细胞氧化损伤而改善神经元细胞毒性作用，继而为防治动物大脑氧化损伤提供新策略及研发饲料添加剂奠定理论基础。 |
| 关键词: 天然化合物 异鼠李素 神经元细胞 神经毒性 氧化损伤 |
| DOI：10.11841/j.issn.1007-4333.2023.11.13 |
| 投稿时间：2022-12-13 |
| 基金项目:国家自然科学基金青年项目(32202862)；黑龙江省自然科学基金优秀青年项目(YQ2021C028) |
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| Effect of isorhamnetin on 6-hydroxydopamine-induced neuronal cytotoxicity and protection against oxidative injury |
|
ZNENG Yuwei,YU Langchao,XIA Shijie,HE Yuxi,LV Hongming
|
| (College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China) |
| Abstract: |
| To investigate the effects of isorhamnetin(ISO)on neuronal cytotoxicity and the protective effect of oxidative injury, here, a cellular oxidative damage model by stimulating neuronal cells(SH-SY5Y)with 6-hydroxydopamine(6-OHDA)was established and analyzed the ISO on 6-OHDA-induced neuronal cell viability, apoptosis-related apoptotic proteins, and oxidative damage-related indicators. The results showed that: 1)6-OHDA(300 μmol/L)could significantly reduce neuronal cell viability(P<0. 01), induce cell apoptosis and expression of pro-apoptotic proteins(Caspase-3, Bax), as well as the expression of anti-apoptotic protein Bcl-2. However, ISO treatment could effectively inhibit neuronal cell damage caused by 6-OHDA. 2)6-OHDA could also significantly induce production of cell reactive oxygen species(ROS)(P<0. 01), cause consumption of glutathione(GSH)(P<0. 05), and promote mitochondrial dysfunction, while ISO treatment could efficiently improve the oxidative damage and mitochondrial dysfunction caused by 6-OHDA(P<0. 05). 3)ISO not only significantly increased the expression of antioxidant proteins(GCLC, GCLM, HO-1 and NQO1)by upregulating of the Keap1/Nrf2 signaling pathway(P<0. 05), but also significantly inhibited the expression reduced by 6-OHDA(P<0. 05). In summary, this study clarified that ISO may effectively improve neuronal cytotoxicity by upregulating the Keap1/Nrf2 antioxidant signaling pathway to inhibit 6-OHDA-induced apoptosis, oxidative stress and mitochondrial damage, thereby providing new strategies for preventing and treating animal brain oxidative damage and laying a theoretical foundation for the development of feed additives. |
| Key words: natural compounds isorhamnetin neuronal cells neurotoxicity oxidative injury |
