SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury.
Ischemia reperfusion (IR) injury is harmful to skeletal muscles and causes mitochondrial oxidative stress. Pterostilbene (PTE), an analogue of resveratrol, has organic protective effects against oxidative stress. However, no studies have investigated whether PTE can protect against IR-related skeletal muscular injury. In this study, we sought to evaluate the protective effect of PTE against IR-related skeletal muscle injury and to determine the mechanisms in this process. Male Sprague-Dawley rats were pretreated with PTE for a week and then underwent limb IR surgery. The IR injury induced segmental necrosis and apoptosis, myofilament disintegration, thicker interstitial spaces, and inflammatory cell infiltration. Furthermore, mitochondrial respiratory chain activity in the muscular tissue was inhibited, methane dicarboxylic aldehyde concentration and myeloperoxidase activity were up-regulated, and superoxide dismutase was down-regulated after IR. However, these effects were significantly inhibited by PTE in a dose-dependent manner. The mechanism underlying IR injury is attributed to the down-regulation of silent information regulator 1 (SIRT1)-FOXO1/p53 pathway and the increase of the Bax/Bcl2 ratio, Cleaved poly ADP-ribose polymerase 1, Cleaved Caspase 3, which can be reversed with PTE. Furthermore, EX527, an SIRT1 inhibitor, counteracted the protective effects of PTE on IR-related muscle injury. In conclusion, PTE has protective properties against IR injury of the skeletal muscles. The mechanism of this protective effect depends on the activation of the SIRT1-FOXO1/p53 signaling pathway and the decrease of the apoptotic ratio in skeletal muscle cells.
Department of Orthopaedics, The 82th Hospital of PLA, 100# Jiankang Road, Huaian, 213002, China. yedongcheng888@126.com.|Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China. yedongcheng888@126.com.
Yedong
Y
Cheng
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
Shouyin
S
Di
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
Chongxi
C
Fan
Department of Orthopaedics, The 82th Hospital of PLA, 100# Jiankang Road, Huaian, 213002, China.
Liping
L
Cai
Department of Orthopaedics, The 82th Hospital of PLA, 100# Jiankang Road, Huaian, 213002, China.
Chao
C
Gao
Department of Orthopaedics, The 82th Hospital of PLA, 100# Jiankang Road, Huaian, 213002, China.
Peng
P
Jiang
Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Wei
W
Hu
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
Zhiqiang
Z
Ma
Department of Aerospace Medicine, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Shuai
S
Jiang
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, 83 Wenhua Road, Shenyang, 110016, China.
Yushu
Y
Dong
Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Tian
T
Li
Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Guiling
G
Wu
Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Jianjun
J
Lv
Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China. yang200214yy@163.com.
Yang
Y
Yang
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D013267:Stilbenes; C107773:pterostilbene; D013482:Superoxide Dismutase; D053148:Caspase 3; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
Ischemia reperfusion injury; Mitochondrial function; Pterostilbene; Silent information regulator 1; Skeletal muscle