Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury.
BACKGROUND
Pathophysiological states that produce intestinal ischemia/reperfusion injury (I/R) initiate an inflammatory cascade and cause ileus. The aims of this study were to investigate the local cellular responses and molecular mechanisms, which contribute to intestinal dysmotility after selective intestinal I/R injury.


METHODS
ACI rats were subjected to 75 min SMA clamp-induced ischemia followed by reperfusion and were killed at 0 min, 30 min, and 24 hr. Whole mounts of the jejunum were used to immunohistochemically quantify alterations in leukocytes, and circular muscle strips were used to assess organ bath muscle function. Muscularis and mucosa extracts were isolated from the intestine and used for reverse transcription assisted polymerase chain reaction mRNA measurements of granulocyte-colony stimulating factor and interleukin-6, and for determination of nuclear factor kappa B and Stat3 activation.


RESULTS
Intestinal I/R injury resulted in the significant recruitment of neutrophils and monocytes into the intestinal muscularis and a functional suppression in jejunal circular muscle contractions. These I/R injury induced cellular responses were preceded by the molecular activation of nuclear factor kappa B, up-regulation of granulocyte colony-stimulating factor and interleukin-6 mRNA and phosphorylation of the downstream signaling and transcription factor Stat3.


CONCLUSIONS
I/R injury evokes a molecular and cellular inflammatory response within the intestinal muscularis that is associated with a subsequent decrease in intestinal motility.
Hierholzer
C
C
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Kalff
J C
JC
Audolfsson
G
G
Billiar
T R
TR
Tweardy
D J
DJ
Bauer
A J
AJ
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007422:Intestines / Q000098:blood supply* / Q000503:physiopathology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011912:Rats, Inbred ACI; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D016179:Granulocyte Colony-Stimulating Factor