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Apoptosis

, Volume 21, Issue 8, pp 905–916 | Cite as

SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury

  • Yedong Cheng
  • Shouyin Di
  • Chongxi Fan
  • Liping Cai
  • Chao Gao
  • Peng Jiang
  • Wei Hu
  • Zhiqiang Ma
  • Shuai Jiang
  • Yushu Dong
  • Tian Li
  • Guiling Wu
  • Jianjun Lv
  • Yang Yang
Article

Abstract

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.

Keywords

Pterostilbene Skeletal muscle Ischemia reperfusion injury Silent information regulator 1 Mitochondrial function 

Notes

Acknowledgments

This work was supported by National Natural Science Foundation of China (81500263) and China Postdoctoral Science Foundation (2015M572681).

Compliance with ethical standards

Conflicts of interest

The authors declare no competing financial interests.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yedong Cheng
    • 1
    • 2
  • Shouyin Di
    • 3
  • Chongxi Fan
    • 3
  • Liping Cai
    • 1
  • Chao Gao
    • 1
  • Peng Jiang
    • 1
  • Wei Hu
    • 2
  • Zhiqiang Ma
    • 3
  • Shuai Jiang
    • 4
  • Yushu Dong
    • 5
  • Tian Li
    • 2
  • Guiling Wu
    • 2
  • Jianjun Lv
    • 2
  • Yang Yang
    • 2
  1. 1.Department of OrthopaedicsThe 82th Hospital of PLAHuaianChina
  2. 2.Department of Biomedical EngineeringThe Fourth Military Medical UniversityXi’anChina
  3. 3.Department of Thoracic Surgery, Tangdu HospitalThe Fourth Military Medical UniversityXi’anChina
  4. 4.Department of Aerospace MedicineThe Fourth Military Medical UniversityXi’anChina
  5. 5.Department of NeurosurgeryGeneral Hospital of Shenyang Military Area CommandShenyangChina

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