微RNA-669f-5p/脱氧胞苷酸脱氨酶轴介导七氟醚诱导老年小鼠认知功能障碍的机制研究

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yuan-Ping Zhong, Chao Zhang, Xue Zheng, Dong-Qin Chen, Xu Fang, Yu Zhang, Zhao-Qiong Zhu
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引用次数: 0

摘要

目的研究微RNA(miRNA)-669f-5p/脱氧胞苷酸脱氨酶(Dctd)轴在七氟烷诱导老年小鼠认知功能障碍中的作用:将66只C57BL/6J小鼠随机分为七氟烷组和对照组。七氟醚组的小鼠使用 3.4% 的七氟醚进行麻醉,而对照组的小鼠则在相同时间内进行空气处理。研究随后进行了生物信息学测序以及体外和体内验证:结果:七氟烷组小鼠的认知能力明显受损,空间学习和记忆能力均下降。实验剂量的 miR-669f-5p 激动剂对小鼠吸入七氟烷后的认知功能无明显影响,但抑制 miR-669f-5p 的表达可减轻小鼠的认知功能障碍。根据生物信息学测序的结果,miR-669f-5p/Dctd和toll样受体(TLR)信号通路可能是导致吸入七氟醚后认知功能障碍的关键miRNA、基因和通路。吸入七氟烷后,老年小鼠海马中的miR-669f-5p表达明显增加,上调/抑制其表达可增加/减少海马中的TLR表达。此外,miR-669f-5p 可通过与 Dctd 基因的 3'untranslated 区域结合来降低该基因的表达:结论:miR-669f-5p/Dctd轴在七氟烷诱导老年小鼠认知功能障碍的过程中发挥了重要作用,为进一步开发预防和治疗七氟烷麻醉相关认知功能障碍的治疗策略提供了新方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanism research on microRNA-669f-5p/deoxycytidylate deaminase axis mediating sevoflurane-induced cognitive dysfunction in aged mice.

Objective: To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice.

Methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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