C57Bl/6 小鼠可作为研究人类骨骼肌线粒体功能的合适模型。

The C57Bl/6 mouse serves as a suitable model of human skeletal muscle mitochondrial function.

机构信息

Institute of Physiology and Zurich Center for Integrative Human Physiology, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

出版信息

Exp Physiol. 2013 Apr;98(4):908-21. doi: 10.1113/expphysiol.2012.070037. Epub 2012 Nov 23.

Abstract

It is debatable whether differences in mitochondrial function exist across skeletal muscle types and whether mouse skeletal muscle mitochondrial function can serve as a valid model for human skeletal muscle mitochondrial function. The aims of this study were to compare and contrast three different mouse skeletal muscles and to identify the mouse muscle that most closely resembles human skeletal muscle respiratory capacity and control. Mouse quadriceps (QUAD(M)), soleus (SOL(M)) and gastrocnemius (GAST(M)) skeletal muscles were obtained from 8- to 10-week-old healthy mice (n = 8), representing mixed, oxidative and glycolytic muscle, respectively. Skeletal muscle samples were also collected from young, active, healthy human subjects (n = 8) from the vastis lateralis (QUAD(H)). High-resolution respirometry was used to examine mitochondrial function in all skeletal muscle samples, and mitochondrial content was quantified with citrate synthase activity. Mass-specific respiration was higher across all respiratory states in SOL(M) versus both GAST(M) and QUAD(H) (P < 0.01). When controlling for mitochondrial content, however, SOL(M) respiration was lower than GAST(M) and QUAD(H) (P < 0.05 and P < 0.01, respectively). When comparing respiratory capacity between mouse and human muscle, QUAD(M) exhibited only one different respiratory state when compared with QUAD(H). These results demonstrate that qualitative differences in mitochondrial function exist between different mouse skeletal muscles types when respiratory capacity is normalized to mitochondrial content, and that skeletal muscle respiratory capacity in young, healthy QUAD(M) does correspond well with that of young, healthy QUAD(H).

摘要

线粒体功能在不同的骨骼肌类型之间是否存在差异,以及小鼠骨骼肌的线粒体功能是否可以作为人类骨骼肌线粒体功能的有效模型,这一点存在争议。本研究的目的是比较和对比三种不同的小鼠骨骼肌,并确定最接近人类骨骼肌呼吸能力和控制的小鼠肌肉。从 8 至 10 周龄的健康小鼠(n = 8)中获得股四头肌(QUAD(M))、比目鱼肌(SOL(M))和腓肠肌(GAST(M))骨骼肌,分别代表混合、氧化和糖酵解肌肉。还从年轻、活跃、健康的人类受试者的外侧股(QUAD(H))中收集骨骼肌样本。使用高分辨率呼吸测定法检查所有骨骼肌样本中的线粒体功能,并通过柠檬酸合酶活性定量线粒体含量。与 GAST(M)和 QUAD(H)相比,SOL(M)在所有呼吸状态下的比质量呼吸都更高(P < 0.01)。然而,当控制线粒体含量时,SOL(M)的呼吸比 GAST(M)和 QUAD(H)低(P < 0.05 和 P < 0.01,分别)。当比较小鼠和人类肌肉的呼吸能力时,QUAD(M)与 QUAD(H)相比仅表现出一种不同的呼吸状态。这些结果表明,当将呼吸能力归一化为线粒体含量时,不同的小鼠骨骼肌类型之间存在线粒体功能的定性差异,并且年轻、健康的 QUAD(M)的骨骼肌呼吸能力与年轻、健康的 QUAD(H)非常吻合。

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