title: Protective roles of hydroxyethyl starch 130/0.4 in intestinal inflammatory response and oxidative stress after hemorrhagic shock and resuscitation in rats.
abstract: This study was designed to determine the effects of various resuscitation fluids on intestinal injuries after hemorrhagic shock and resuscitation (HS/R) and to determine the potential mechanisms. We induced HS by bleeding male Sprague-Dawley rats to a blood pressure of 30 to 40 mmHg for 60 min. Sixty minutes later, the rats were killed (HS group) or immediately resuscitated with L-isomer lactated Ringer's solution (HS + LR group), shed blood (HS + BL group), or hydroxyethyl starch (HS + HES group) to maintain the blood pressure to the original value during the 60-min resuscitation period. Three hour after resuscitation, bacterial translocation (BT), intestinal permeability, ileal levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, malondialdehyde (MDA), oxidized and reduced glutathione (GSH and GSSG), myeloperoxidase (MPO) activity, nuclear factor (NF)-kappaB, activator protein (AP)-1 activation, and ileal microscopic and ultrastructural histological changes were measured. Another experiment was designed for survival study of 24 h. HES 130/0.4 solution was as effective as shed blood, required a small volume requirement to restore circulation, and significantly reduced HS/R-induced ileal villous morphological injuries with an anti-inflammatory effect, as reflected by a reduction of TNF-alpha, IL-6, MPO activity, and NF-kappaB activation. In addition, HES resuscitation also reduced intestinal permeability and BT and caused less oxidative stress as reflected by a reduction of MDA, GSSG/GSH and AP-1 activation along with restored GSH, whereas shed blood couldn't. No significant difference was observed in outcome among groups. HES 130/0.4 resuscitation prevents HS/R induced intestinal injury by modulating inflammatory response and preventing oxidative stress in a rat model of hemorrhagic shock. These physiological protective effects appear to be mediated by down-regulation of the transcription factor NF-kappaB and AP-1.
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Li
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D007410:Intestinal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; D020011:Protective Agents