长链非编码 RNA HOXA11-AS 通过调节 miR-98-5p/EphA4 对七氟醚诱导的神经元凋亡和炎症反应的影响。
Effects of lncRNA HOXA11-AS on Sevoflurane-Induced Neuronal Apoptosis and Inflammatory Responses by Regulating miR-98-5p/EphA4.
机构信息
Department of Anesthesiology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, 650118 Yunnan, China.
Department of Ultrasound, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, 650118 Yunnan, China.
出版信息
Mediators Inflamm. 2023 Apr 5;2023:7750134. doi: 10.1155/2023/7750134. eCollection 2023.
OBJECTIVE
To explore the molecular mechanism of sevoflurane-induced neurotoxicity and to determine whether lncRNA HOXA11-AS affects sevoflurane-induced neuronal apoptosis and inflammation by regulating miR-98-5p/EphA4.
METHODS
Morris water maze (MWM) test was used to detect the learning and memory ability of rats, HE staining was used to observe hippocampal pathology, TUNEL staining was used to detect the level of neuronal apoptosis, and RT-qPCR was used to detect the expression of HOXA11-AS, miR-98-5p, IL-6, IL-1, and TNF-. At the same time, the contents of IL-6, IL-1, and TNF- in serum were detected by ELISA. The expressions of apoptosis-related proteins EphA4, Bax, Cleaved caspase 3, and Bcl-2 were detected by Western blot. The dual-luciferase gene reporter verified the targeting relationship between HOXA11-AS and miR-98-5p and the targeting relationship between miR-98-5p and EphA4.
RESULTS
The expression of HOXA11-AS was observed in sevoflurane-treated rats or cells and promoted neuronal apoptosis and inflammation. HOXA11-AS was knocked out alone, or miR-98-5p was overexpressed which attenuates neuronal apoptosis and inflammatory inflammation after sevoflurane treatment. Furthermore, knockdown of HOXA11-AS alone was partially restored by knockdown of miR-98-5p or overexpression of EphA4.
CONCLUSION
Inhibition of lncRNA HOXA11-AS attenuates sevoflurane-induced neuronal apoptosis and inflammatory responses via miR-98-5p/EphA4.
目的
探讨七氟醚诱导神经毒性的分子机制，并确定长链非编码 RNA（lncRNA）HOXA11-AS 是否通过调节 miR-98-5p/EphA4 影响七氟醚诱导的神经元凋亡和炎症。
方法
采用 Morris 水迷宫（MWM）试验检测大鼠学习记忆能力，HE 染色观察海马病理，TUNEL 染色检测神经元凋亡水平，RT-qPCR 检测 HOXA11-AS、miR-98-5p、IL-6、IL-1β 和 TNF-α 的表达。同时，采用 ELISA 法检测血清中 IL-6、IL-1β 和 TNF-α 的含量。Western blot 检测凋亡相关蛋白 EphA4、Bax、Cleaved caspase 3 和 Bcl-2 的表达。双荧光素酶基因报告验证 HOXA11-AS 与 miR-98-5p 的靶向关系以及 miR-98-5p 与 EphA4 的靶向关系。
结果
观察到七氟醚处理的大鼠或细胞中 HOXA11-AS 的表达，并促进神经元凋亡和炎症。单独敲除 HOXA11-AS，或单独过表达 miR-98-5p 均可减轻七氟醚处理后的神经元凋亡和炎症。此外，单独敲低 HOXA11-AS 部分被 miR-98-5p 的敲低或 EphA4 的过表达所恢复。
结论
抑制 lncRNA HOXA11-AS 通过 miR-98-5p/EphA4 减轻七氟醚诱导的神经元凋亡和炎症反应。
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