title: Polydatin ameliorates injury to the small intestine induced by hemorrhagic shock via SIRT3 activation-mediated mitochondrial protection.
abstract: Previously, we demonstrated that sirtuin (SIRT)1 plays vital roles in the small intestine (SI), protecting against severe hemorrhagic shock (HS), and that polydatin (PD) can attenuate SI injury via SIRT1 activation.
  
  
  
  To explore the role of SIRT3 and mitochondria in SI injury after HS, and explore SIRT3 as a therapeutic target of PD in HS.
  
  
  
  An H2O2-induced model of oxidative stress and an HS model were created in IEC-6 cells and Sprague-Dawley rats, respectively. Protein content and activity of SIRT1/3 and SOD2, acetylated-SOD2 level, and mitochondrial morphology/function were determined.
  
  
  
  Expression and activity of SIRT1/3 were reduced in SI tissue and IEC-6 cells after HS or oxidative stress, accompanied by an increased acetylated-SOD2 level and damaged mitochondria. Treatment with PD or resveratrol restored SIRT1/3 activity considerably, restored SIRT1/3 expression slightly, and reduced acetylated-SOD2 levels, which lead to elevated SOD2 activity and ameliorated mitochondrial function. The addition of 3-TYP (SIRT3 inhibitor) partially blocked the mitochondrial-protective effects of PD, but did not affect increased SIRT1 activity.
  
  
  
  The SIRT3-SOD2 signaling pathway is involved in mitochondrial dysfunction induced by HS. PD attenuates mitochondrial dysfunction via activation of the SIRT3-SOD2 pathway, and may be a new approach for HS treatment.
authors.affiliation: a Department of Critical Care Medicine , Nanfang Hospital, Southern Medical University , Guangzhou , P. R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: a Department of Critical Care Medicine , Nanfang Hospital, Southern Medical University , Guangzhou , P. R. China.
authors.forename: Yating
authors.initials: Y
authors.lastname: Yang
authors.affiliation: b The First People's Hospital of Chenzhou, Department of Critical Care Medicine , Institute of Translational Medicine , Chenzhou , P. R. China.
authors.forename: Xingui
authors.initials: X
authors.lastname: Dai
authors.affiliation: c Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology , Southern Medical University , Guangzhou , P. R. China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Xu
authors.affiliation: b The First People's Hospital of Chenzhou, Department of Critical Care Medicine , Institute of Translational Medicine , Chenzhou , P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: a Department of Critical Care Medicine , Nanfang Hospital, Southern Medical University , Guangzhou , P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: c Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology , Southern Medical University , Guangzhou , P. R. China.
authors.forename: Ke-Seng
authors.initials: KS
authors.lastname: Zhao
authors.affiliation: a Department of Critical Care Medicine , Nanfang Hospital, Southern Medical University , Guangzhou , P. R. China.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D037761:Sirtuins / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D005960:Glucosides; D006861:Hydrogen Peroxide; D000077185:Resveratrol; D037761:Sirtuins; D013267:Stilbenes; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C000607791:SIRT3 protein, rat; C058229:polydatin
keywords: Deacetylation; SIRT3; SOD2; hemorrhagic shock; intestinal injury; mitochondrial dysfunction