隔日间断禁食通过稳定线粒体嵴结构增强大鼠缺氧耐力的机制研究OA
Mechanism of intermittent fasting every other day enhancing hypoxia tolerance in rats via stabilization of mitochondrial cristae structure
目的 探讨隔日间断禁食对大鼠缺氧耐力的影响,并初步探讨其机制.方法 选取体质量250～300 g的健康雄性SD大鼠,随机分为对照组(Con组)、对照缺氧组(Con+H组)、间断禁食组(IF组)和间断禁食缺氧组(IF+H组).Con组和Con+H组正常饲养;IF组和IF+H组采用隔日禁食方式,5 d内累计禁食72 h,禁食期间完全剥夺食物但不限制饮水;每日定时检测各组大鼠体质量、血糖和血酮水平;饲养 5d后,将Con+H组和IF+H组置于7 620m模拟高空缺氧环境中停留 24 h,观察大鼠存活率;通过透射电镜观察各组大鼠心肌组织线粒体形态,统计受损线粒体数量;采用Western blotting检测心肌组织中线粒体质量控制相关蛋白(生成、融合、分裂)及ATP合成相关蛋白的表达水平;采用ATP 含量化学发光法检测各组大鼠心肌组织中ATP含量.结果 IF+H组大鼠存活率显著高于Con+H组(P<0.01).隔日禁食干预后,大鼠心肌组织中线粒体生成与融合相关蛋白表达显著升高,缺氧条件下受损线粒体数量明显少于Con+H组(P<0.01),ATP含量显著高于Con+H组(P<0.01).结论 隔日间断禁食通过促进线粒体生成与融合,增加OPA1 蛋白表达,稳定线粒体嵴结构,从而增强大鼠心肌组织的耐缺氧能力.
Objective To investigate the effect of alternate-day intermittent fasting on hypoxic tolerance in rats and to preliminarily explore its underlying mechanisms.Methods Healthy male SD rats weighing 250-300 g were randomly divided into four groups:control group(Con group),control+hypoxia group(Con+H group),intermittent fasting group(IF group),and intermittent fasting+hypoxia group(IF+H group).The Con and Con+H groups were fed normally.The IF and IF+H groups underwent alternate-day fasting,accumulating 72 h of fasting over 5 d,during which food was completely deprived but water was available ad libitum.Body mass,blood glucose,and blood ketone levels were measured daily at fixed times.After 5 d of feeding,the Con+H and IF+H groups were exposed to a simulated high-altitude hypoxic environment at 7 620 m for 24 h to observe survival rates.Myocardial tissue mitochondrial morphology was observed using transmission electron microscopy,and the number of damaged mitochondria was quantified.Western blotting was used to detect the expression levels of proteins related to mitochondrial quality control(biogenesis,fusion and fission)and ATP synthesis.ATP content in myocardial tissue was measured using a chemiluminescent ATP assay kit.Results The survival rate of the IF+H group was significantly higher than that of the Con+H group(P<0.01).After alternate-day fasting intervention,the expression of mitochondrial biogenesis and fusion-related proteins in rat myocardial tissue was significantly increased.Under hypoxic conditions,the number of damaged mitochondria in the IF+H group was significantly lower than that in the Con+H group(P<0.01),and ATP content was significantly higher(P<0.01).Conclusion Alternate-day intermittent fasting enhances myocardial hypoxic tolerance in rats by promoting mitochondrial biogenesis and fusion,increasing OPA1 protein expression,and stabilizing mitochondrial cristae structure.
焦博;白云刚;赵汝舟;陈祥宁;张琳;余志斌
空军军医大学航空航天生理学教研室,陕西 西安 710032空军军医大学航空航天生理学教研室,陕西 西安 710032空军军医大学航空航天生理学教研室,陕西 西安 710032军事医学研究院,北京 100071空军军医大学航空航天生理学教研室,陕西 西安 710032空军军医大学航空航天生理学教研室,陕西 西安 710032
医药卫生
间断禁食缺氧线粒体线粒体嵴GTP磷酸水解酶腺苷三磷酸心室线粒体动力学
intermittent fastinghypoxiamitochondriamitochondrial cristaeGTP phosphohydrolasesadenosine triphosphateheart ventriclesmitochondrial dynamics
《空军军医大学学报》 2026 (1)
33-38,6
国家自然科学基金面上项目(32371237)
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