Suzhou Medical College of Soochow University, Suzhou, China.
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Fundam Clin Pharmacol. 2024 Dec;38(6):1031-1044. doi: 10.1111/fcp.13023. Epub 2024 Jul 4.
To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice.
Sixty-six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air-treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation.
The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR-669f-5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR-669f-5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR-669f-5p/Dctd and the toll-like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR-669f-5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR-669f-5p could reduce the expression of the Dctd gene by binding to its 3'untranslated region.
The miR-669f-5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia.
探讨微小 RNA（miRNA）-669f-5p/脱氨酶（Dctd）轴在七氟醚诱导老年小鼠认知功能障碍中的作用。
将 66 只 C57BL/6J 小鼠纳入实验模型，随机分为七氟醚组和对照组。七氟醚组小鼠用 3.4%七氟醚麻醉，对照组小鼠同期空气处理。然后使用生物信息学测序以及体外和体内验证进行研究。
七氟醚组小鼠在空间学习和记忆能力下降方面表现出明显的认知功能障碍。实验剂量的 miR-669f-5p 激动剂吸入七氟醚后对认知功能无明显影响，但抑制 miR-669f-5p 的表达可减轻损伤。基于生物信息学测序的结果，miR-669f-5p/Dctd 和 Toll 样受体（TLR）信号通路可能是七氟醚吸入后术后认知功能障碍的关键 miRNA、基因和通路。吸入七氟醚后，老年小鼠海马中 miR-669f-5p 的表达明显增加，上调/抑制其表达可增加/减少海马中 TLR 的表达。此外，miR-669f-5p 可通过结合其 3'非翻译区降低 Dctd 基因的表达。
miR-669f-5p/Dctd 轴在七氟醚诱导老年小鼠认知功能障碍中起重要作用，为进一步开发与七氟醚麻醉相关的认知功能障碍的预防和治疗策略提供了新方向。
