2025 年第 5 期 第 20 卷

烟酰胺核糖改善马方综合征小鼠肌少症的作研究

Effect of nicotinamide ribose on sarcopenia in Marfan syndrome mice

作者：洪诗瑶张燕红姚可欣靳姝慧张帆韩迎春张聪聪

英文作者：Hong Shiyao Zhang Yanhong Yao Kexin Jin Shuhui Zhang Fan Han Yingchun Zhang Congcong

单位：首都医科大学附属北京安贞医院北京市心肺血管疾病研究所心血管基础与转化医学研究中心，北京100029

英文单位：Research Center of Basic and Translational Cardiovascular Medicine Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：马方综合征；肌少症；烟酰胺核糖；线粒体

英文关键词：Marfansyndrome;Sarcopenia;Nicotinamideribose；Mitochondrion

• 摘要：

• 目的 探讨在马方综合征（MFS）模型小鼠中补充烟酰胺核糖（NR）对线粒体合成和MFS小鼠肌少症的影响。方法 选取3月龄的雄性野生型和原纤维蛋白1（FBN1）C1039G/+转基因（FBN1 TG）小鼠各10只，对胫骨前肌肌内注射心脏毒素制备骨骼肌损伤模型。分析2组小鼠的新生肌纤维面积、线粒体数量及体积，检测线粒体功能相关基因的表达水平。在诱导分化的C2C12肌母细胞培养基中分别加入NR（NR组）或等体积的磷酸盐缓冲液（对照组）处理细胞，观察2组肌细胞生成素基因的表达、肌纤维的面积、细胞中线粒体的含量。术后第15天分析小鼠新生肌纤维面积。结果 FBN1 TG小鼠的腓肠肌质量/肌肉长度比值与胫骨前肌质量/肌肉长度比值均低于野生型小鼠，且心脏毒素损伤骨骼肌前后肌纤维的横截面面积均小于野生型小鼠（均P＜0.001），表现为肌少症。术后第10天，FBN1 TG小鼠新生骨骼肌中线粒体数量、线粒体相关基因的表达少于/低于野生型小鼠(均P<0.001)。NR组C2C12肌母细胞中分化相关基因肌细胞生成素的表达、融合形成的肌纤维的阳性面积、细胞中线粒体的含量均高于对照组（均P＜0.001）。术后第15天，NR处理的FBN1 TG小鼠的骨骼肌肌纤维横截面面积大于0.9%氯化钠注射液处理的FBN1 TG小鼠［(836±52)μm2比（550±36）μm2］（t=9.017，P＜0.001）。结论 NR可促进线粒体合成和肌纤维的形成，从而改善MFS小鼠肌少症的表型。

• Objective To investigate the effects of nicotinamide ribose (NR) supplementation on mitochondrial synthesis and sarcopenia in Marfan syndrome (MFS) mice. Methods Ten 3-month-old male wild type and 10 FBN1C1039G/+ transgenic (FBN1 TG) mice were selected to establish a skeletal muscle injury model by intramuscular injection of cardiotoxin into the tibial anterior muscle. The area of neonatal muscle fiber, the number and volume of mitochondria were analyzed, and the expression levels of mitochondrial function-related genes were detected. NR (NR group) or equal volume of phosphate buffer (control group) was added to the culture medium of induced C2C12 myoblasts. The expression of myogenin gene, the area of muscle fiber and the content of mitochondria in cells were observed. The area of newly formed muscle fibers was analyzed on the 15th day after operation. Results The ratios of gastrocnemius muscle mass to muscle length and tibialis anterior muscle mass to muscle length of FBN1 TG mice were lower than those of wild type mice, and the cross-sectional areas of muscle fibers before and after cardiac toxin injury were smaller than those of wild type mice (all P<0.001). It was manifested as sarcopenia. On day 10 after surgery, the number of mitochondria and the expression of mitochondria-related genes in the newborn skeletal muscle of FBN1 TG mice were less/lower than those of wild type mice (all P<0.001). The expression of myogenin, the positive area of myofibers and the content of mitochondria in C2C12 myoblasts in NR group were higher than those in control group (all P<0.001). On postoperative day 15, the cross-sectional area of muscle fibers in skeletal muscle of NR-treated FBN1 TG mice was larger than that of FBN1 TG mice treated with 0.9% sodium chloride injection ［(836±52)μm2 vs (550±36)μm2］(t=9.017, P<0.001). Conclusion NR can improve the phenotype of sarcopenia in MFS mice by promoting mitochondrial synthesis and muscle fiber formation.