Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Neuroimmunomodulation. 2022;29(2):117-127. doi: 10.1159/000519124. Epub 2021 Dec 2.
Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified.
ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay.
1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19.
Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.
异氟烷（ISO）在发育过程中可能引起神经元凋亡和突触紊乱，并损害长期学习和记忆功能。本研究旨在通过体外和体内试验研究 H19 的功能，并确定其进一步的机制。
建立 ISO 细胞模型和大鼠模型，并鉴定活性氧（ROS）。通过 MTT 和流式细胞仪检测 HT22 细胞的活力和凋亡。通过 Morris 水迷宫测试分析 ISO 对空间学习和记忆能力的神经毒性。采用定量 PCR 验证 H19 的表达。通过酶联免疫吸附试验鉴定炎症指标的浓度。
1.5%和 2% ISO 导致 HT22 细胞的神经毒性，并增加 H19 的表达。沉默 H19 可改善 ISO 的这些不良影响。干扰 H19 通过抑制改良神经严重程度评分、抑制逃逸潜伏期、提高目标区域的距离和时间、控制 ROS 和炎症，发挥神经保护作用。miR-17-5p 可能是 H19 的一种有前途的竞争内源性 RNA。miR-17-5p 的表达在 ISO 组中降低，并被 H19 的缺失所逆转。
我们的体外和体内试验结果表明，HT22 的缺失通过积累 miR-17-5p 来调节认知和炎症的神经保护作用。
