| 王海涛,杨雯茜,刘玉倩.有氧运动激活SLC7A11/GPx4通路抑制线粒体铁死亡预防老年小鼠肌少症的作用[J].中国康复医学杂志,2025,(4):501~507 |
| 有氧运动激活SLC7A11/GPx4通路抑制线粒体铁死亡预防老年小鼠肌少症的作用 点此下载全文 |
| 王海涛 杨雯茜 刘玉倩 |
| 岭南师范学院运动与健康研究所，广东省湛江市，524048 |
| 基金项目：广东省教育科学规划课题(2023GXJK371）；2023年度湛江市科技局项目（2023B01168） |
| DOI：10.3969/j.issn.1001-1242.2025.04.004 |
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| 摘要： |
| 摘要
目的：阐明溶质载体家族7成员11（solute carrier protein 7，family member 11，SLC7A11）/谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPx4）调控的铁死亡（ferroptosis）通路在有氧运动改善肌少症中的作用，为运动防治肌少症提供新的作用靶点。
方法：52周龄无特定病原体（specific pathogen free，SPF）级C57BL/6雄性小鼠20只，随机分为老年对照组（old control，OC）和老年运动组（old exercise，OE），每组10只。1周适应性运动后进行16w递增负荷中等强度运动（1—2w 14m/min，3—4w 15m/min，5—10w 16m/min，11—16w 17m/min，60min/d，坡度为0°）。取腓肠肌制作超薄透射电镜切片。谷胱甘肽（glutathione， GSH）、肌糖原、非血红素铁（non-heme iron）含量采用分光光度计法。血清铁蛋白（serum ferritin，SF），线粒体8-羟基脱氧鸟苷（8-hydroxy-2 deoxyguanosine，8-OHdG）和4-羟基壬烯酸（4-Hydroxynonena，4-HNE）测试采用酶联免疫吸附测定（enzyme-linked immunosorbent assay，ELISA）法。Western blot检测腓肠肌铁代谢相关蛋白表达：GPx4、SLC7A11、膜铁转运蛋白1（ferroportin 1， FPN1）、铁蛋白重链（ferritin heavy chain 1，FTH1）。
结果：①与对照组小鼠相比，运动组小鼠股四头肌、腓肠肌湿重和抓力显著增加（P<0.01）；老年运动组线粒体嵴排列整齐致密，肌丝明暗带清晰；老年对照组腓肠肌线粒体嵴断裂、呈空泡状或固缩，出现典型的铁死亡特征。②与对照组小鼠相比，老年运动组机体SF和腓肠肌铁含量均下降（P<0.01）。③老年运动组小鼠腓肠肌4—HNE和线粒体过氧化损伤标志物8-OHdG显著低于对照组（P<0.01）。老年运动组小鼠腓肠肌GSH含量显著高于对照组（P<0.01）。④老年运动组小鼠腓肠肌SLC7A11、GPx4和FPN1、FTH1表达量显著高于对照组（P<0.01）。
结论：适度有氧运动可以通过激活SLC7A11/GPx4通路，抑制线粒体铁死亡，预防增龄引发的肌少症。 |
| 关键词：铁死亡 肌少症 线粒体 有氧运动 |
| Aerobic exercise activates SLC7A11/GPx4 pathway to inhibit mitochondrial ferroptosis and prevent sarcopenia in aging mice Download Fulltext |
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| Institute of Exercise and Health Promotion，School of Physical Education and Sports Science， Lingnan Normal University， Zhanjiang， 524048 |
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| Abstract: |
| Abstract
Objective： To elucidate the role of solute carrier protein 7， family member 11 （SLC7A11）/Glutathione peroxidase 4（glutathione peroxidase 4，GPx4） regulated ferroptosis pathway in the improvement of sarcopenia through aerobic exercise, and to identify a new target for the prevention and treatment of sarcopenia with exercise.
Method： Twenty 52-week-old Specific pathogen Free （SPF） C57BL/6 male mice were randomly divided into the old control group （OC） and the old exercise group （OE）. There were 10 mice in each group. Following one week of adaptive exercise， moderate-intensity exercise with incremental load was implemented as follows: 14 m/min at 1—2 weeks， 15 m/min at 3—4 weeks， 16m/min at 5—10weeks， 17m/min at 11—16weeks， 60min/d， all with a slope of 0°. Gastrocnemius was harvested for ultrathin electron microscope sections. The levels of Glutathione （GSH）， muscle glycogen and non-heme iron （non-heme iron） were measured by spectrophotometer. The serum ferritin （SF）， mitochondrial 8-hydroxy-2 deoxyguanosine （8-OHdG） and 4-Hydroxynonena （4-HNE） were measured by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression of iron metabolism-related proteins， such as GPx4， SLC7A11， ferroportin 1 （FPN1） and ferritin heavy chain 1 （FTH1） in gastrocnemius muscle.
Result： ①Compared with OC， the wet weights of quadriceps femoris and gastrocnemius in OE were significantly increased（P<0.01）. In the exercise group， mitochondrial cristae arranged neatly and densely， and the light and dark bands of myofilaments were clear. In the aged control group， the mitochondrial cristae of gastrocnemius muscle were disrupted， vacuolated or pyknotic， showing typical features of ferroptosis. ② The SF and the iron content of gastrocnemius muscle were decreased in OE （P<0.01）. ③ The levels of 4-HNE and 8-OHdG in gastrocnemius muscle of OE were significantly lower than those of OC （P<0.01）. The GSH content in gastrocnemius of OE was significantly higher than that of OC （P<0.01）. ④ The expressions of SLC7A11， GPx4， FPN1 and FTH1 in gastrocnemius muscle of OE were significantly higher than those of OC （P<0.01）.
Conclusion： Moderate aerobic exercise can prevent age-related sarcopenia by activating the SLC7A11/GPx4 pathway and inhibiting mitochondrial ferroptosis. |
| Keywords:ferroptosis sarcopenia mitochondria aerobic exercise |
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