Yang Qiaoyun, Li Chunqiu, Chen Qingwei
Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Cardiovasc Med. 2022 Apr 14;9:789331. doi: 10.3389/fcvm.2022.789331. eCollection 2022.
Oxidative stress and impaired autophagic flux play important roles in the development of peripheral artery disease (PAD). SS31 is considered an important antioxidant peptide and autophagy regulator. We aimed to investigate the role of SS31 in PAD myopathy and its possible mechanism both and .
A hind limb ischemia (HLI) model was established with old C57BL/6 (14-month-old) mice. Mice in the SS31 group were intraperitoneally injected with SS31 (3 mg/kg) for 4 weeks. We examined skeletal muscle function and histomorphology, autophagy-related protein levels and reactive oxygen species (ROS) content. For the experiments, after C2C12 myotubes were treated with CoCl, SS31, and chloroquine (CQ) or rapamycin (RAPA), we measured ROS content, autophagy-related protein levels and antioxidant enzyme expression.
SS31 treatment effectively enhanced the recovery of skeletal muscle function, alleviated skeletal muscle injury and suppressed mitochondrial ROS production in ischemic limbs. SS31 reduced apoptosis and oxidative stress, and SS31 restored impaired autophagic flux by inhibiting the AKT-mTOR pathway. studies showed that SS31 restored autophagic flux and improved oxidative stress in C2C12 cells. Moreover, phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) levels were reduced.
These experiments indicated that SS31 can inhibit oxidative stress by restoring autophagic flux to reverse hypoxia-induced injury and .
氧化应激和自噬通量受损在周围动脉疾病（PAD）的发展中起重要作用。SS31被认为是一种重要的抗氧化肽和自噬调节剂。我们旨在研究SS31在PAD肌病中的作用及其可能的机制。
用老年C57BL/6（14个月大）小鼠建立后肢缺血（HLI）模型。SS31组小鼠腹腔注射SS31（3mg/kg），持续4周。我们检测了骨骼肌功能和组织形态学、自噬相关蛋白水平和活性氧（ROS）含量。对于细胞实验，在用氯化钴、SS31、氯喹（CQ）或雷帕霉素（RAPA）处理C2C12肌管后，我们测量了ROS含量、自噬相关蛋白水平和抗氧化酶表达。
SS治疗有效促进了骨骼肌功能的恢复，减轻了骨骼肌损伤，并抑制了缺血肢体线粒体ROS的产生。SS31减少了细胞凋亡和氧化应激，并且SS31通过抑制AKT-mTOR途径恢复了受损的自噬通量。细胞实验表明，SS31恢复了C2C12细胞的自噬通量并改善了氧化应激。此外，磷酸化AKT（p-AKT）和磷酸化mTOR（p-mTOR）水平降低。
这些实验表明，SS31可以通过恢复自噬通量来抑制氧化应激，以逆转缺氧诱导的损伤。
