三萜烯酸 B 通过调节神经元和小胶质细胞中 mir-329-3p 的不同方式对七氟醚诱导的认知障碍发挥保护作用。
Protective role of trametenolic acid B against sevoflurane-induced cognitive impairments by its different regulatory modalities of mir-329-3p in neurons and microglia.
机构信息
Department of Anesthesiology, Weifang Medical University, Weifang, 261053, Shandong, China.
Department of Gynecology, Affiliated Hospital of Weifang Medical University, Weifang, 261031, Shandong, China.
出版信息
Mol Med. 2022 Jul 3;28(1):77. doi: 10.1186/s10020-022-00477-6.
BACKGROUND
Postoperative cognitive dysfunction induced by anesthetics commonly occurs in elderly patients. This study aimed to evaluate the protective role of trametenolic acid B (TAB) in sevoflurane-induced cognitive impairments, and explore the underlying mechanisms.
METHODS
Animal and cell experiments were performed in rats, differentiated PC12 and HAPI cells by exposing to 2% sevoflurane for 5 h. Different concentration (20, 40 and 80 µg/mL) of TAB was administrated in rats and cells. The cognitive function of rats was evaluated using the Morris water maze test and fear conditioning test. The cell proliferation and apoptosis were investigated using a CCK-8 assay and the flow cytometry. Pro-inflammatory cytokines in microglia were measured using ELISA kits. A miRNA microarray assay was conducted to screen differentially expressed miRNAs by TAB in both PC12 and HAPI cells. The luciferase reporter assay and western blot assay were used to assess the E2F1/CCNA2 and NF-κB pathways.
RESULTS
TAB significantly alleviated sevoflurane-induced cognitive impairments in rats, improved PC12 cell viability, and inhibited the neuroinflammation of HAPI cells. miR-329-3p was downregulated in PC12 cells but upregulated in HAPI cells by TAB treatment, which mediated the effects of TAB on neurotoxicity and neuroinflammation. E2F1 and NF-κB P65 were two targets of miR-329-3p, and the E2F1/CCNA2 and NF-κB pathways were inhibited by miR-329-3p in PC12 and HAPI cells, respectively.
CONCLUSIONS
All the results provide evidence for the protective role of TAB against sevoflurane-induced cognitive impairments, which was achieved by alleviating neurotoxicity and neuroinflammation through differentially regulating miR-329-3p in neurons and microglia.
背景
麻醉引起的术后认知功能障碍在老年患者中很常见。本研究旨在评估三萜烯酸 B（TAB）在七氟醚诱导的认知障碍中的保护作用，并探讨其潜在机制。
方法
在大鼠、分化的 PC12 和 HAPI 细胞中进行动物和细胞实验，用 2%七氟醚暴露 5 小时。在大鼠和细胞中给予不同浓度（20、40 和 80μg/ml）的 TAB。使用 Morris 水迷宫试验和恐惧条件试验评估大鼠的认知功能。使用 CCK-8 测定法和流式细胞术研究细胞增殖和凋亡。ELISA 试剂盒测定小胶质细胞中的促炎细胞因子。通过 TAB 在 PC12 和 HAPI 细胞中进行 miRNA 微阵列分析，筛选差异表达的 miRNA。荧光素酶报告基因检测和 Western blot 检测用于评估 E2F1/CCNA2 和 NF-κB 途径。
结果
TAB 显著减轻了大鼠七氟醚诱导的认知障碍，提高了 PC12 细胞活力，并抑制了 HAPI 细胞的神经炎症。TAB 处理后，PC12 细胞中的 miR-329-3p 下调，而 HAPI 细胞中的 miR-329-3p 上调，miR-329-3p 介导了 TAB 对神经毒性和神经炎症的影响。E2F1 和 NF-κB P65 是 miR-329-3p 的两个靶点，miR-329-3p 在 PC12 和 HAPI 细胞中分别抑制了 E2F1/CCNA2 和 NF-κB 途径。
结论
所有结果都为 TAB 对七氟醚引起的认知障碍的保护作用提供了证据，这是通过在神经元和小胶质细胞中差异调节 miR-329-3p 来减轻神经毒性和神经炎症来实现的。
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