11β-羟化类固醇脱氢酶敲除对高脂饮食喂养小鼠认知功能的影响  

Effect of 11β-hydroxysteroid dehydrogenase knockout on cognitive function in high-fat diet-induced obese mice

作　　者：曹清 秦丽 刘娟[1] CAO Qing;QING Li;LIU Juan(Division of Geriatric Endocrinology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院老年医学科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2023年第8期1047-1054,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金面上项目(81871106,82071584)。

摘　　要：目的:探究11β-羟化类固醇脱氢酶1(11β-hydroxysteroid dehydrogenase,11β-HSD1)基因敲除对小鼠整体代谢和认知功能的影响。方法:将C57BL/6J为遗传背景的野生对照组及11β-HSD1基因敲除组各15只小鼠高脂喂养20周,代谢笼评估能量代谢,行为学评估观察小鼠认知功能,电镜评估海马体的线粒体结构,免疫荧光及PCR确定其认知功能、线粒体功能相关基因及炎症基因的变化。结果:11β-HSD1基因敲除能够提高高脂喂养小鼠学习和记忆能力,改善握力,改善海马体的微结构、线粒体含量变多,认知相关基因、线粒体呼吸功能相关基因上调,炎症相关基因改变。结论:11β-HSD1敲除后高脂饮食喂养小鼠认知功能显著改善,握力显著提高,可能是治疗认知功能障碍的有效靶点。Objective:To investigate the effect of 11β-hydroxysteroid dehydrogenase(11β-HSD1)gene knockout on the metabolism and cognitive function of mice.Methods:A total of 15 mice each in the C57BL/6J genetic background wild control group and 11β-HSD1 gene knockout group were fed with high fat for 20 weeks.We then assessed energy metabolism by metabolic cage,observed their cognitive function by behavioral evaluation,evaluated hippocampus mitochondria by electron microscope,and determined changes in cognitive function,mitochondrial function-related genes,and inflammatory genes by immunofluorescence and RT-PCR.Results:The 11β-HSD1 gene knockout in showed the enhanced learning and memory ability,increased grip strength,improved hippocampal microstructure,amplified mitochondrial content,up-regulated the genes related to cognition and mitochondrial respiratory function,and changed the inflammatory genes.Conclusion:Our study demonstrated that knockout 11β-HSD1 significantly improved cognitive function and grip strength mice fed high-fat diet,therefore may be an effective target for the treatment of cognitive dysfunction.

关 键 词：11β-羟化类固醇脱氢酶1 认知功能 海马体 线粒体 

分 类 号：R329.26[医药卫生—人体解剖和组织胚胎学]