title: Ulinastatin attenuates oxidation, inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation.
abstract: OBJECTIVE
  The role of Ulinastatin in neuronal injury after cardiopulmonary resuscitation has not been elucidated. We aim to evaluate the effects of Ulinastatin on inflammation, oxidation, and neuronal injury in the cerebral cortex after cardiopulmonary resuscitation.
  
  
  METHODS
  Ventricular fibrillation was induced in 76 adult male Wistar rats for 6 min, after which cardiopulmonary resuscitation was initiated. After spontaneous circulation returned, the rats were split into two groups: the Ulinastatin 100,000 unit/kg group or the PBS-treated control group. Blood and cerebral cortex samples were obtained and compared at 2, 4, and 8 h after return of spontaneous circulation. The protein levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assayed using an enzyme-linked immunosorbent assay, and mRNA levels were quantified via real-time polymerase chain reaction. Myeloperoxidase and Malondialdehyde were measured by spectrophotometry. The translocation of nuclear factor-κB p65 was assayed by Western blot. The viable and apoptotic neurons were detected by Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
  
  
  RESULTS
  Ulinastatin treatment decreased plasma levels of TNF-α and IL-6, expression of mRNA, and Myeloperoxidase and Malondialdehyde in the cerebral cortex. In addition, Ulinastatin attenuated the translocation of nuclear factor-κB p65 at 2, 4, and 8 hours after the return of spontaneous circulation. Ulinastatin increased the number of living neurons and decreased TUNEL-positive neuron numbers in the cortex at 72 h after the return of spontaneous circulation.
  
  
  CONCLUSIONS
  Ulinastatin preserved neuronal survival and inhibited neuron apoptosis after the return of spontaneous circulation in Wistar rats via attenuation of the oxidative stress response and translocation of nuclear factor-κB p65 in the cortex. In addition, Ulinastatin decreased the production of TNF-α, IL-6, Myeloperoxidase, and Malondialdehyde.
authors.affiliation: Department of Emergency Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Chun Lin
authors.initials: CL
authors.lastname: Hu
authors.forename: Jin Ming
authors.initials: JM
authors.lastname: Xia
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Xiao Xing
authors.initials: XX
authors.lastname: Liao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhan
authors.forename: Gang
authors.initials: G
authors.lastname: Dai
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Jing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014693:Ventricular Fibrillation / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D015850:Interleukin-6; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; C028665:urinastatin