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
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南京医科大学第一附属医院老年医学科

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国家自然科学基金面上项目(81871106,82071584)


Effect of 11β-hydroxysteroid dehydrogenase knockout on cognitive function in high-fat diet-induced obese mice
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Division of Geriatric Endocrinology,the First Affiliated Hospital of Nanjing Medical University

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    摘要:

    目的:探究11β-羟化类固醇脱氢酶(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:本研究显示,11β-HSD1敲除后认知功能显著改善,握力显著提高,可能是治疗认知功能障碍的有效靶点。

    Abstract:

    [Abstract] Objective: To investigate the effect of 11β-hydroxysteroid dehydrogenase (11β-hydroxysteroid dehydrogenase, 11β-HSD1) gene knockout on the metabolism and cognitive function of mice. Methods: 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: 11β-HSD1 knockout mice showed 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 gene significantly improved cognitive function and grip strength in high-fat diet-induced obese mice, therefore 11β-HSD1 may be an effective target for the treatment of cognitive dysfunction.

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  • 收稿日期:2023-03-30
  • 最后修改日期:2023-05-11
  • 录用日期:2023-08-09
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