Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARg/NF-kB/IL-6 signaling pathway  

作　　者：Yongbing Deng Xue Jiang Xiaoyan Deng Hong Chen Jie Xu Zhaosi Zhang Geli Liu Zhu Yong Chengfu Yuan Xiaochuan Sun Changdong Wang 

机构地区：[1]Department of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University,Yixueyuan Road#1,Chongqing,400016,PR China [2]Department of Neurosurgery of the Chongqing Emergency Medical Center,Jiankang Road#1,Chongqing,400014,PR China [3]Department of Biochemistry and Molecular Biology,Molecular Medicine and Cancer Research Center,Chongqing Medical University,Yixueyuan Road#1,Chongqing,400016,PR China [4]Department of Microbiology and Molecular Genetics,School of Medicine,University of California,Irvine,Irvine,CA 92697,USA [5]College of Medical Science,China Three Gorges University,Yichang,Hubei,443002,PR China

出　　处：《Genes & Diseases》2020年第2期253-265,共13页基因与疾病（英文）

基　　金：This study was financially supported by the Education Commission of Chongqing in China(Grant No.KJQN201800124 to Y.B.Deng and Grant No.CY170402 to C.D.Wang);the Natural Science Foundation of Chongqing China(Grant No.cstc2016jcyjA0220 to X.Jiang and Grant No.cstc2014jcyjA10024 to C.D.Wang);Doctoral Program of Higher Education of China(20125503120015 to C.D.Wang).

摘　　要：Traumatic brain injury(TBI)is the major cause of high mortality and disability rates worldwide.Pioglitazone is an activator of peroxisome proliferator-activated receptor-gamma(PPARγ)that can reduce inflammation following TBI.Clinically,neuroinflammation after TBI lacks effective treatment.Although there are many studies on PPARγin TBI animals,only few could be converted into clinical,since TBI mechanisms in humans and animals are not completely consistent.The present study,provided a potential theoretical basis and therapeutic target for neuroinflammation treatment after TBI.First,we detected interleukin-6(IL-6),nitric oxide(NO)and Caspase-3 in TBI clinical specimens,confirming a presence of a high expression of inflammatory factors.Western blot(WB),quantitative real-time PCR(qRTPCR)and immunohistochemistry(IHC)were used to detect PPARγ,IL-6,and p-NF-kB to identify the mechanisms of neuroinflammation.Then,in the rat TBI model,neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone(PPARγactivator)or T0070907(PPARγinhibitor),and PPARγ,IL-6 and p-NF-kB were detected again by qRT-PCR,WB and immunofluorescence(IF).The obtained results revealed that:1)increased expression of IL-6,NO and Caspase-3 in serum and cerebrospinal fluid in patients after TBI,and decreased PPARγin brain tissue;2)pioglitazone could improve neurobehavioral and reduce brain edema in rats after TBI;3)the protective effect of pioglitazone was achieved by activating PPARγand reducing NF-kB and IL-6.The neuroprotective effect of pioglitazone on TBI was mediated through the PPARγ/NF-kB/IL-6 pathway.

关 键 词：KEYWORDS Traumatic brain injury IL-6 PIOGLITAZONE PPARγ p-NF-kB 

分 类 号：R651.15[医药卫生—外科学]