title: The protective effects of N-n-butyl haloperidol iodide on myocardial ischemia-reperfusion injury in rats by inhibiting Egr-1 overexpression.
abstract: OBJECTIVE
  Our previous studies have shown that N-n-butyl haloperidol iodide (F(2)) can antagonize myocardial ischemia/reperfusion (I/R) injury by blocking intracellular Ca(2+) overload. The present study is to test the hypothesis that the protective effects of F(2) on myocardial I/R injury is mediated by downregulating Egr-1 expression.
  
  
  METHODS
  The Sprague-Dawley rat myocardial I/R model and cardiomyocyte hypoxia/reoxygenation (H/R) model were established. With antisense Egr-1 oligodeoxyribonucleotide (ODN), the relationship between Egr-1 expression and myocardial I/R injury was investigated. Hemodynamic parameters, myeloperoxidase (MPO), cardiac troponin I (cTnI) and tumor necrosis factor-alpha (TNF-alpha) were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Egr-1 mRNA and protein expressions were examined by Northern-blot and Western-blot analyses.
  
  
  RESULTS
  Treatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of myocardial tissues and cells. Meanwhile, treatment with F(2) significantly inhibited the overexpression of Egr-1 mRNA and protein in myocardial tissues and cells. Consistent with downregulation of Egr-1 expression by F(2), inflammation and other damages were significantly relieved evidenced by the amelioration of hemodynamics, the reduction in myocardial MPO activity as well as the decrease in leakage of cTnI and release of TNF-alpha from cardiomyocyte.
  
  
  CONCLUSIONS
  These results suggested that the overexpression of Egr-1 was causative in myocardial I/R or H/R injury, and F(2) could protect myocardial tissues and cells from I/R or H/R injury, which was largely due to the inhibition of Egr-1 overexpression.
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ganggang
authors.initials: G
authors.lastname: Shi
authors.forename: Jinhong
authors.initials: J
authors.lastname: Zheng
authors.forename: Zhao
authors.initials: Z
authors.lastname: Tang
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Lv
authors.forename: Fuxiao
authors.initials: F
authors.lastname: Guo
authors.forename: Qiangyong
authors.initials: Q
authors.lastname: Jia
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015394:Molecular Structure; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C482574:N-n-butyl haloperidol iodide; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D006220:Haloperidol