Protective roles of hydroxyethyl starch 130/0.4 in intestinal inflammatory response and survival in rats challenged with polymicrobial sepsis.
BACKGROUND
The gut is considered an important target organ of injury after severe insult such as sepsis, trauma and shock. Hydroxyethyl starch (HES) 130/0.4 has been developed to improve the pharmacokinetics of current medium molecular weight HES solutions. We investigated the protective effects of HES 130/0.4 on intestinal inflammatory response and survival in a rat polymicrobial sepsis model induced by cecal ligation and puncture.


METHODS
Animals were treated with HES 130/0.4 or saline at 4, 10, 16 or 22 h after the induction of sepsis or sham-operation and were sacrificed 2 h after resuscitation. Intestines were harvested for measurement of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-10 and macrophage inflammatory protein-2 (MIP-2) production by EELISA; intercellular adhesion molecule-1 (ICAM-1) mRNA expression by reverse-transcription PCR; nuclear factor-kappa B (NF-kappaB) by electrophoretic mobility shift assay; neutrophil sequestration by myeloperoxidase (MPO) assay; intestinal permeability by fluorescein isothiocyanate-labeled dextran assay. In addition, the role of HES 130/0.4 in rat survival was observed.


RESULTS
Intestinal permeability was significantly decreased after HES 130/0.4 administration in septic rats, which was associated with a reduction in inflammatory mediators and NF-kappaB activation. Furthermore, early administration of HES 130/0.4 after septic insult resulted in greater decrease in inflammatory mediators. In addition, HES 130/0.4 co-administrated with antibiotics not HES 130/0.4 alone greatly improved the survival of septic rats.


CONCLUSIONS
HES 130/0.4 reduced intestinal permeability by modulating inflammatory response and had a promising effect on survival together with antibiotics under septic conditions.
Feng
Xiaomei
X
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, P. R. China.
Liu
Jian
J
Yu
Min
M
Zhu
Sihai
S
Xu
Jianguo
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism*; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy*; D015996:Survival Rate
D000900:Anti-Bacterial Agents; D006895:Hydroxyethyl Starch Derivatives; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase