Department of Neurology, Yan-an Hospital of Kunming City, Kunming, China.
Department of Emergency Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Bioengineered. 2022 Mar;13(3):7065-7081. doi: 10.1080/21655979.2022.2045764.
Resveratrol (Res) is a flavonoid with an antioxidant effect and has been utilized to treat oxidative stress-related illnesses; however, its mechanism remains ambiguous. This research aims to explore whether Res inhibits miR-136-5p expression, increases heme oxygenase 1 (HMOX1) expression, and mitigates oxidative stress and PC12 cell apoptosis triggered by paraquat (PQ). Results showed that PQ dose-dependently increased the expression of miR-136-5p, the apoptosis of PC12 cells, the activities of reactive oxygen species (ROS), and the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), caspase-3, and pro-apoptotic protein Bax. In addition, PQ reduced the expression of anti-apoptotic protein Bcl-2, HMOX1 mRNA and protein, and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) protein and the activity of superoxide dismutase 1 (SOD1) and PC12 cells. After the PQ-treated PC12 cells were administered with different Res concentrations for 24 h, the miR-136-5p expression was dose-dependently decreased. An increase was observed in the activity and survival rate of PC12 cells, the protein and mRNA levels of HMOX1 and Nrf2, and the content of anti-apoptotic protein B-cell lymphoma/leukemia gene-2 (Bcl-2). By contrast, the activities of ROS, LDH, and MDA and the apoptosis of PC12 cells decreased. These findings illustrated that Res could reduce the oxidative stress and apoptosis triggered by PQ and enhance the activity and survival rate of PC12 cells. The underlying mechanism might be correlated with the reduced miR-136-5p expression and the elevated activity of the HMOX1/Nrf2 pathway.
白藜芦醇（Res）是一种具有抗氧化作用的类黄酮，已被用于治疗与氧化应激相关的疾病；然而，其机制仍不清楚。本研究旨在探讨白藜芦醇是否通过抑制 miR-136-5p 的表达、增加血红素加氧酶 1（HMOX1）的表达，来减轻百草枯（PQ）引发的氧化应激和 PC12 细胞凋亡。结果表明，PQ 呈剂量依赖性地上调 miR-136-5p 的表达，促进 PC12 细胞凋亡，增加活性氧（ROS）的产生和乳酸脱氢酶（LDH）、丙二醛（MDA）、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）和促凋亡蛋白 Bax 的水平。此外，PQ 降低了抗凋亡蛋白 B 细胞淋巴瘤/白血病基因-2（Bcl-2）、HMOX1mRNA 和蛋白、核因子红细胞 2 相关因子 2（Nrf2）蛋白和超氧化物歧化酶 1（SOD1）的活性以及 PC12 细胞的活力。用不同浓度白藜芦醇处理 PQ 处理的 PC12 细胞 24 h 后，miR-136-5p 的表达呈剂量依赖性降低。PC12 细胞的活力和存活率增加，HMOX1 和 Nrf2 的蛋白和 mRNA 水平以及抗凋亡蛋白 B 细胞淋巴瘤/白血病基因-2（Bcl-2）的含量增加，而 ROS、LDH 和 MDA 的活性以及 PC12 细胞的凋亡减少。这些发现表明，白藜芦醇可以减轻 PQ 引发的氧化应激和细胞凋亡，增强 PC12 细胞的活力和存活率。其潜在机制可能与 miR-136-5p 表达的降低和 HMOX1/Nrf2 途径的活性升高有关。
