• Zhenhua Zeng, Yating Yang, Xingui Dai, Siqi Xu, Tao Li, Qin Zhang, Ke-Seng Zhao, and Zhongqing Chen.
• a Department of Critical Care Medicine , Nanfang Hospital, Southern Medical University , Guangzhou , P. R. China.
• Expert Opin. Ther. Targets. 2016 Jun 1; 20 (6): 645-52.

BackgroundPreviously, 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.ObjectiveTo explore the role of SIRT3 and mitochondria in SI injury after HS, and explore SIRT3 as a therapeutic target of PD in HS.MethodsAn 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.ResultsExpression 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.ConclusionsThe 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.

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