[Protective effects of vasoactive intestinal peptide on intestinal lesions induced by endotoxic shock in rat].
OBJECTIVE
Vasoactive intestinal peptide (VIP) is a neuro-peptide that can modulate immunity in several aspects. Previous reports showed that VIP attenuates the deleterious consequences of severe infection and septic shock by regulating production of inflammatory cytokines in immune activated cells. Intestine is one of the major organ of immune system and it may trigger multiple organ dysfunction syndrome in sepsis. The present study was planned to study the change of serum TNF-alpha, IL-1beta, IL-10 level and histopathological alteration of intestinal tract, and protective effects of VIP on endotoxic shock in rat.


METHODS
Twenty eight SD rats were randomly divided into 3 groups, including control group (8 rats), LPS shock group (10 rats), and LPS + VIP group (10 rats). Endotoxic shock model was established by administration of a single dose of 10 mg/kg LPS in LPS shock group, a bolus of 5 nmol VIP intravenous injection following LPS in LPS + VIP group. The rats in the control group were given the same volume of normal saline injection. Blood samples were taken at time points of 1, 2, 4, and 6 hours after intervention from each group for measuring the level of TNF-alpha, IL-1beta and IL-10 by ELISA. Pathological changes of the intestine were observed by light microscope and electron microscope at the animals death or at the end of the experiment.


RESULTS
Serum TNF-alpha, IL-1beta and IL-10 levels elevated at each time point in LPS shock group and LPS + VIP group (P < 0.05 or P < 0.01). TNF-alpha concentration reached the peak level 2 h after LPS injection; IL-1beta and IL-10 increased continuously till the end of the experiment. In LPS + VIP group, TNF-alpha and IL-1beta elevated slightly and IL-10 increased significantly as compared with LPS shock group (P < 0.01). Leukocyte infiltration, ischemia, segmental hemorrhage or necrosis appeared in intestine under light microscope and cell swelling, cytoplasmic vacuoles and organelle damage were observed under electron microscope. However, pathological changes in LPS + VIP group were milder than those in LPS group.


CONCLUSIONS
VIP improved endotoxic shock-associated histopathological alteration of intestine, down-regulated pro-inflammatory cytokines production and up-regulated anti-inflammatory cytokines. These effects may suggest a protective mechanism of VIP in septic shock. VIP is a potential immunoregulatory substance in treatment of septic shock.
Zhang
Yu-cai
YC
Pediatric Institute for Critical Illness Research, Critical Care Center of Children's Hospital, Shanghai Jiaotong University, Shanghai 200040, China.
Yang
Li-ping
LP
Tang
Ding-hua
DH
Zhang
Yu-ming
YM
D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007422:Intestines / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*
D015415:Biomarkers; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014660:Vasoactive Intestinal Peptide