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.