Abstract:

Objective To explore the characteristics of antioxidant stress of muscle tissue after aging based on the nuclear factor E2-related factor 2（Nrf2） dependent antioxidant pathway， and to clarify the effect of the dynamic balance between reactive oxygen species （ROS） production and antioxidation in the age-related sarcopenia. Methods Twenty four C57BL/6J （C57） male mice were randomly divided into 3-month-old group （3 M group）， 12-month-old group （12 M group） and 22-month-old group （22 M group）. The soleus muscle tissue of mice was taken， and the skeletal muscle mass index （SMI） was calculated. The pathomorphology of muscle tissue of the mice in various groups was observed by HE staining. The ROS levels of mice in various groups were detected by 2'，7'-dichlorodihydrofluorescein diacetate（DCFH-DA） fluorescence probe method， the mRNA expression levels of eroxisome proliferators-activated receptor-γ coactivator-1α （PGC-1α）， Nrf2 and antioxidant stress genes in muscle tissue of the mice in various groups were detected by real-time fluorescence quantitative（RT-qPCR） method，and the protein expression levels of Nrf2 in muscle tissue of the mice in various groups were detected by Western blotting method. Results Compared with 3 M group， the cross-sectional area of soleus muscle fibers of the mice in 12 M group was increased， the number of nuclei in some muscle fibers was increased， and some muscle fibers showed denaturation changes；the SMI value was decreased， but the difference was not statistically significant （P>0.05）；the level of ROS was increased （P<0.05），the expression level of Nrf2 mRNA had no significant difference（P>0.05）， the expression level of PGC-1α mRNA was significantly increased （P<0.01），the expression levels of Nqol， Cat， Gclc， Sod1 and Sod2 mRNA were significantly increased （P<0.01）， and the expression level of Nrf2 protein was significantly decreased （P<0.01）. Compared with 12 M group， the white muscle fibers of soleus muscle of the mice in 22 M group were increased， the morphology was irregular， the number of nuclei of muscle fibers was increased and the phenomenon of nuclear translocation occurred， the gap between muscle cells was increased， the number of cells was decreased， and the SMI value was decreased， but the difference was not statistically significant （P>0.05）； the level of ROS in muscle tissue was significantly increased （P<0.01）， the expression levels of Nrf2 mRNA was significantly increased （P<0.01）， the expression levels of Nqol， Cat， Sod1 and Sod2 mRNA were significantly increased （P<0.05 or P<0.01）， while the expression level of Gclc mRNA was decreased （P<0.05）， and the expression level of Nrf2 protein was significantly increased （P<0.01）. Conclusion The soleus muscle of aging mice shows sarcopenia phenotype. The soleus muscle with oxidative metabolism as the main has certain characteristics of antioxidant stress ability， which is closely related to the enhancement of Nrf2 dependent antioxidant pathway.

Key words: Sarcopenia, Skeletal muscle, Nuclear factor E2-related factor, Mitochondrial homeostasis