Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria

作     者：Li Li Hong-Ping Tan Cheng-Yong Liu Lin-Tao Yu Da-Nian Wei Zi-Chen Zhang Kui Lu Ke-Sen Zhao Marc Maegele Dao-Zhang Cai Zheng-Tao Gu 

作者机构：Department of Treatment Center for Traumatic Injuriesthe Third Affiliated Hospital of Southern Medical UniversityAcademy of Orthopedics·Guangdong ProvinceGuangzhouGuangdong ProvinceChina Department of PathophysiologySouthern Medical UniversityGuangdong Provincial Key Laboratory of Shock and Microcirculation ResearchGuangzhouGuangdong ProvinceChina Department of Epilepsy SurgeryGuangdong Sanjiu Brain HospitalGuangzhouGuangdong ProvinceChina Department of Emergencythe Third Affiliated Hospital of Southern Medical UniversityAcademy of Orthopedics·Guangdong ProvinceGuangzhouGuangdong ProvinceChina Department of Traumatology and Orthopedic SurgeryCologne-Merheim Medical Center(CMMC)University Witten/Herdecke(UW/H)Campus Cologne-MerheimCologneGermany Department of Orthopedicsthe Third Affiliated Hospital of Southern Medical UniversityAcademy of Orthopedics·Guangdong ProvinceGuangzhouGuangdong ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2019年第14卷第9期

页      面：1573-1582页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 100215[医学-康复医学与理疗学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,No.81501690(to ZTG) the Scientific Research Staring Foundation for Talent Introduction for Southern Medical University(to MM) 

主　　题：nerve regeneration traumatic brain injury polydatin mitochondria endoplasmic reticulum stress SIRT1 reactive oxygen species p38 mitochondrial membrane potential mitochondrial permeability transition pore lateral fluid percussion neural regeneration 

摘      要：Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To investigate the protective effect of polydatin after traumatic brain injury,a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults.Rat models were intraperitoneally injected with polydatin(30 mg/kg)or the SIRT1 activator SRT1720(20 mg/kg,as a positive control to polydatin).At 6 hours post-traumatic brain injury insults,western blot assay was used to detect the expression of SIRT1,endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side.Flow cytometry was used to analyze neuronal mitochondrial superoxide,mitochondrial membrane potential and mitochondrial permeability transition pore opened.Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy.Our results showed that after treatment with polydatin,release of reactive oxygen species in neuronal mitochondria was markedly reduced;swelling of mitochondria was alleviated;mitochondrial membrane potential was maintained;mitochondrial permeability transition pore opened.Also endoplasmic reticulum stress related proteins were inhibited,including the activation of p-PERK,spliced XBP-1 and cleaved ATF6.SIRT1 expression and activity were increased;p38 phosphorylation and cleaved caspase-9/3 activation were inhibited.Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury.These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria.The mechanisms may be linked to increased SIRT1 expression and activity,which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016.