International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 244-252 http://medscipublisher.com/index.php/ijccr 246 weakened under the influence of sepsis. Studies have found that the expression of SIRT3 in lung and kidney tissues is significantly reduced during sepsis, which is related to the increased acetylation and inactivation of FOXO3a and the decreased expression of SOD2, thereby leading to a decline in antioxidant capacity (Figure 1) (Wu et al., 2023; Fan et al., 2025). Figure 1 The effect of SNG on mitochondrial protection and apoptosis of KTECs (Adopted from Fan et al., 2025) Image caption: (A) changes in mitochondrial morphology (n = 10 in each group); (B) changes in mitochondrial density (n = 10 in each group); (C) the level of MDA (n = 10 in each group); (D) the level of SOD (n = 10 in each group); (E) the level of ROS (n = 10 in each group); (F) apoptosis of KTECs (n = 10 in each group); (G) apoptotic rate in KTECs (n = 10 in each group); The ratio of female mice to male mice in each group is 1:1; Compared with the sham group, ***p < 0.001; compared with the CLP group, ##p < 0.01, ###p < 0.001 (n = 10 in each group) (Adopted from Fan et al., 2025) In addition, in the experimental models of intestinal and cardiac damage caused by sepsis, dynamic changes in FOXO3a activation and SOD2 transcription can be observed. These changes are usually accompanied by an increase in ROS production, indicating that the inhibition of this pathway is not only a result of sepsis but may also actively promote tissue damage. Just as Zou et al. (2019) discovered, the expression of SIRT1 and FOXO3a in septic intestinal tissues is strictly controlled, which indicates that oxidative stress directly affects the activity of pathways. 3.2 Network imbalance leads to mitochondrial damage, ROS accumulation and cell death The imbalance of the SIRT3-FOXO3a-SOD2 network can aggravate oxidative stress and also cause problems with mitochondrial function, which is the main cause of cell death in sepsis. Reduced SIRT3 activity can affect the deacetylation of FOXO3a, inhibit its entry into the cell nucleus and the transcription of downstream genes such as SOD2. A reduction in SOD2 will weaken the mitochondrial clearance ability of ROS and accelerate oxidative damage. Wu et al. (2023) confirmed that overexpression of SIRT3 could reverse these conditions by restoring the functions of FOXO3a and SOD2 to reduce pyroptosis in septic lung tissue. Similarly, in the T-2 toxin-induced rat cardiac fibrosis model (as an oxidative damage model), inhibition of the SIRT3/FOXO3a/SOD2 axis aggravates mitochondrial damage and cell death. It is notable that the increase of ROS and mitochondrial swelling are closely related to the weakening of this pathway, which also indicates that it plays a key role in maintaining mitochondrial integrity (Qiao et al, 2024).
RkJQdWJsaXNoZXIy MjQ4ODYzNA==