title: Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis.
abstract: BACKGROUND
  Sepsis with brain dysfunction has contributed to an increase risk of morbidity and mortality. In its pathophysiology, both autophagy and nuclear factor κB (NF-κB) have been suggested to play important roles. Based on the fact that crosstalk between autophagy and NF-κB, two stress-response signaling pathways, has been detected in other pathophysiological processes, this study was undertaken to explore the process of autophagy in the hippocampus of septic rats and the role NF-κB plays in the regulation of autophagy during the process.
  
  
  METHODS
  Cecal ligation and puncture (CLP) or a sham operation was conducted on male Wistar rats. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of the NF-κB signaling pathway, or a vehicle control, was used to treat with the rats 2 h before the CLP operation. Hematoxylin-eosin staining and biological signal recording was used to measure the morphological and physiological signs of hippocampal dysfunction. An electron microscope was used to observe autophagosome formation and lysosome activation in the hippocampus after CLP. Western blotting and immune histochemistry were used to detect the hippocampus levels of NF-κB and essential proteins involved in formation of the autophagosome (microtubule-associated protein light chain 3 (LC3), Beclin1, Lamp-1, and Rab7).
  
  
  RESULTS
  Compared with sham-operated rats, the CLP rats showed decreasing mean arterial pressure (MAP), increasing heart rate (HR), and pathological histological changes. CLP rats exhibited not only increased vacuolization through electron micrographs but also increased LC3-II, decreased Beclin1, LAMP-1, and Rab7 through the immunofluorescence and Western blot. However, PDTC + CLP rats revealed that inhibition of the NF-κB signal axis by PDTC increased the levels of LC3-II, Beclin1, LAMP-1, and Rab7 and improved physiological function including blood pressure and heart rate.
  
  
  CONCLUSIONS
  The autophagy process during the hippocampus of CLP rats might be blocked by the activation of NF-κB signaling pathway. Inhibition of NF-κB signaling pathway could enhance the completion of autophagy with a neuroprotective function in septic brains.
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. syj412811@163.com.
authors.forename: YunJie
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. quyi712002@163.com.|Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China. quyi712002@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. hanyue80@163.com.|Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China. hanyue80@163.com.
authors.forename: FengYan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China. lihuafeng@scu.edu.cn.|Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. lihuafeng@scu.edu.cn.
authors.forename: HuaFeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. mudz@scu.edu.cn.|Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China. mudz@scu.edu.cn.|Department of Pediatrics and Neurology, University of California, San Francisco, CA, 94143, USA. mudz@scu.edu.cn.
authors.forename: DeZhi
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. hxlixihong@126.com.
authors.forename: XiHong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001343:Autophagy; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D002432:Cecum / Q000293:injuries; D006339:Heart Rate; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010588:Phagosomes / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics; D013859:Thiocarbamates / Q000627:therapeutic use
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid