Xie Jiacheng, Yang Qiuyue, Zeng Xueliang, Zeng Qi, Xiao Hai
Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Department of Pharmacology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
PeerJ. 2025 Jan 29;13:e18876. doi: 10.7717/peerj.18876. eCollection 2025.
Ischemic stroke (IS) is an important cause of death worldwide. Dihydromyricetin (DHM) has been reported to have neuroprotective potential, but its role and mechanism in IS have not been fully elucidated. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the safe dose of DHM in BV2 microglia and its applicability in OGD/R-treated cells. The mechanism of action of DHM was explored by RT-qPCR, ELISA, luciferase reporter gene assay and western blotting. DHM dose-dependently enhanced BV2 cell viability post-OGD/R and attenuated inflammation and oxidative stress. The protective effects of DHM were found to be mediated through the downregulation of SNHG17, which in turn modulated miR-452-3p expression. miR-452-3p was identified as a negative regulator of pro-inflammatory CXCR4, a direct target whose expression was inversely affected by SNHG17. The interaction between SNHG17 and miR-452-3p was further confirmed by RNA pull-down assays. Furthermore, manipulation of the SNHG17/miR-452-3p/CXCR4 axis was shown to modulate the NF-κB signaling pathway as evidenced by changes in phosphorylation levels. In conclusion, our findings elucidate a novel DHM-mediated neuroprotective mechanism in microglial cells involving the SNHG17/miR-452-3p/CXCR4 regulatory axis. This axis attenuates OGD/R-induced inflammatory and oxidative stress, suggesting a therapeutic potential for DHM in conditions characterized by such pathological processes.
缺血性中风（IS）是全球范围内重要的死亡原因。据报道，二氢杨梅素（DHM）具有神经保护潜力，但其在IS中的作用和机制尚未完全阐明。采用MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）法测定DHM在BV2小胶质细胞中的安全剂量及其在氧糖剥夺/复氧（OGD/R）处理细胞中的适用性。通过逆转录定量聚合酶链反应（RT-qPCR）、酶联免疫吸附测定（ELISA）、荧光素酶报告基因测定和蛋白质免疫印迹法探索DHM的作用机制。DHM呈剂量依赖性地提高OGD/R后BV2细胞的活力，并减轻炎症和氧化应激。发现DHM的保护作用是通过下调SNHG17介导的，而SNHG17又调节了miR-452-3p的表达。miR-452-3p被鉴定为促炎趋化因子受体4（CXCR4）的负调节因子，CXCR4是SNHG17直接靶向的基因，其表达受到SNHG17的反向影响。RNA下拉试验进一步证实了SNHG17与miR-452-3p之间的相互作用。此外，如磷酸化水平的变化所示，对SNHG17/miR-452-3p/CXCR4轴的调控可调节核因子κB（NF-κB）信号通路。总之，我们的研究结果阐明了一种新的DHM介导的小胶质细胞神经保护机制，该机制涉及SNHG17/miR-452-3p/CXCR4调节轴。该轴减轻了OGD/R诱导的炎症和氧化应激，提示DHM在以这种病理过程为特征的疾病中具有治疗潜力。
