title: The therapeutic effects of cholecystokinin octapeptide on rat liver and kidney microcirculation disorder in endotoxic shock.
abstract: OBJECTIVE
  Our previous studies demonstrated that pretreatment with cholecystokinin octapeptide (CCK-8) could alleviate endothelial cell injury and reverse abnormal vascular reactivity as well as reduce LPS-induced inflammation cascades, which suggested that CCK-8 plays a potential role in anti-endotoxic shock. The present study aimed to determine the therapeutic effects of CCK-8 on rat liver and kidney microcirculatory perfusion disorder under endotoxic shock (ES) conditions.
  
  
  METHODS
  Sprague-Dawley rats were induced to lethal endotoxic shock by an injection of LPS. CCK-8 was administered 30 min after LPS injection. Either a specific CCK-1R antagonist or CCK-2R antagonist was injected before CCK-8 treatment. The mean arterial pressure (MAP), liver and kidney microcirculatory perfusion, and heart rate (HR) were recorded with a multi-channel data acquisition system. The serum concentrations of alanine aminotransferase (ALT) and creatinine (Cr) were measured, and the histopathological changes in the liver and kidney were also observed.
  
  
  RESULTS
  Administration of CCK-8 significantly delayed the LPS-induced decreases in not only the liver and kidney microcirculation perfusion but also the HR. The pathology changes induced by LPS in the liver and kidney tissues were significantly mitigated in the LPS + CCK-8 group. The levels of ALT and Cr in the serum of the LPS + CCK-8 group were obviously lower than those in the LPS group. In addition, the specific antagonist at the CCK-2 receptor (CCK-2R) abrogated the action of CCK-8 significantly.
  
  
  CONCLUSIONS
  These results indicated that CCK-8 has potential therapeutic effects on microcirculation failure in an ES rat model via the CCK-2 receptor.
authors.affiliation: a College of Integrated Traditional and Western Medicine , Hebei University of Chinese Medicine , Shijiazhuang , PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Geng
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Shujin
authors.initials: S
authors.lastname: Li
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Ma
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cong
authors.affiliation: b Department of Forensic Medicine , Institute of Basic Medicine, Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002766:Cholecystokinin / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012844:Sincalide / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D009842:Oligopeptides; D002766:Cholecystokinin; D012844:Sincalide
keywords: Cholecystokinin; endotoxic shock; hepatic microcirculation; lipopolysaccharide; renal microcirculation