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Protective Roles of Hydroxyethyl Starch 130/0.4 in Intestinal Inflammatory Response and Oxidative Stress After Hemorrhagic Shock and Resuscitation in Rats

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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)-α, interleukin (IL)-6, malondialdehyde (MDA), oxidized and reduced glutathione (GSH and GSSG), myeloperoxidase (MPO) activity, nuclear factor (NF)-κB, 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-α, IL-6, MPO activity, and NF-κB 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-κB and AP-1.

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Acknowledgments

We thank Prof. Genbao Feng and Mr. Bo Wu for their excellent technical assistance. The study is supported by a grant from special project of Chinese Military Medicine Science and Technology Research”11.5” plan (No. 06Z017).

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  1. Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China

    Pengfei Wang, Yousheng Li & Jieshou Li

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Correspondence to Yousheng Li.

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Wang, P., Li, Y. & Li, J. Protective Roles of Hydroxyethyl Starch 130/0.4 in Intestinal Inflammatory Response and Oxidative Stress After Hemorrhagic Shock and Resuscitation in Rats. Inflammation 32, 71–82 (2009). https://doi.org/10.1007/s10753-009-9105-7

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