miR-103及其靶基因Cav1.2在低氧预适应提升小鼠学习记忆中的表达  

The expression of miR-103 and its target gene Cav1.2 in enhancing learning and memory of hypoxic preconditioning mice

作　　者：翁清明 王蒙 谢伟[1,3] 谢雅彬 WENG Qingmeng;WANG Meng;XIE Wei;XIE Yabin(Inner Mongolia Key Laboratory of Hypoxic Translational Medicine,Baotou Medical College,Baotou 014040;School of Basic Medicine and Forensic Sciences,Baotou Medical College;Neuroscience Institute,School of Medical Technology and Anesthesia,Baotou Medical college)

机构地区：[1]包头医学院内蒙古自治区低氧转化医学重点实验室,内蒙古包头014040 [2]包头医学院基础医学与法医学院 [3]包头医学院医学技术与麻醉学院神经科学研究所

出　　处：《包头医学院学报》2023年第6期10-14,23,共6页Journal of Baotou Medical College

基　　金：国家自然科学基金项目(82071479,31860307);内蒙古自然科学基金项目(2020MS08171);内蒙古自治区高等学校科学研究项目(NJZZ19189);包头医学院创新团队发展计划项目(bycxtd-12);包头医学院花蕾计划项目。

摘　　要：目的:探究miR-103和Cav1.2在低氧预适应改善学习记忆能力中的表达变化,阐明miR-103调控Cav1.2在低氧预适应内源性神经保护中的作用机制。方法:使用ICR雄性小鼠作为实验对象,构建正常组(Control)、低氧组(Hypoxia)、低氧预适应组(HPC),通过Morris水迷宫分别评估各组小鼠的学习记忆能力;通过Real-time PCR和Western bolt技术检测小鼠海马组织中miR-103和Cav1.2的表达变化,通过双荧光素酶报告基因检测miR-103和Cav1.2之间的调控关系。结果:小鼠随着低氧次数的增加,低氧耐受时间显著增强。与Control组相比,HPC组小鼠的潜伏期时间明显降低(P<0.05),目标象限时间的百分比增加(P<0.05),平台穿越次数明显增加(P<0.05)。与Control组相比,HPC组小鼠海马组织中miR-103在第1 d表达下调(P<0.0001)。miR-103-3p通过与Cav1.2的3’UTR结合从而靶向Cav1.2。与Control组相比,HPC组小鼠海马组织中Cav1.2蛋白在第2 d表达升高(P<0.01)。结论:低氧预适应下调miR-103表达,从而上调miR-103下游靶基因Cav1.2的表达,最终提升小鼠低氧耐受能力和认知功能。Objective:To explore the expression changes of miR-103 and Cav1.2 in hypoxic preconditioning to improve learning and memory ability,and to clarify the mechanism of miR-103 regulation of Cav1.2 in hypoxic preconditioning endogenous neuroprotection.Methods:Male ICR mice were used as experimental subjects to construct normal group(Control),Hypoxia group(Hypoxia)and hypoxic preconditioning group(HPC),and morris water maze was used to evaluate the learning and memory ability of each group;Real-time PCR and Western bolt were used to detect the expression changes of miR-103 and Cav1.2 in the hippocampus of mice,and dual luciferase reporter genes were used to detect the regulatory relationship between miR-103 and Cav1.2.Results:With the increase of hypoxia frequency,the tolerance time of hypoxia increased significantly.Compared with the Control group,the latency time of mice in the HPC group was significantly reduced(P<0.05),the percentage of target quadrant time was increased(P<0.05),and the number of platform crossing was significantly increased(P<0.05).Compared with the Control group,the expression of miR-103 in the hippocampus of mice in the HPC group was down-regulated on the first day(P<0.0001).miR-103-3p targets Cav1.2 by binding to the 3’UTR of Cav1.2.Compared with the Control group,the expression of Cav1.2 protein in the hippocampal tissue of mice in the HPC group was increased on day 2(P<0.01).Conclusion:Hypoxia preconditioning down-regulates the expression of miR-103,thus up-regulates the expression of Cav1.2,the downstream target gene of miR-103,and finally improves hypoxia tolerance and cognitive function of mice.

关 键 词：低氧预适应 miR-103 Cav1.2 小鼠 学习记忆 

分 类 号：R394[医药卫生—医学遗传学]