Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury

Background. Pathophysiological states that produce intestinal ischemia/repe rfusion injury (I/R) initiate an inflammatory cascade and cause ileus. The aims of this study were to investigate the local cellular responses and mol ecular mechanisms, which contribute to intestinal dysmotility after selecti ve intestinal I/R injury, Methods. ACI rats were subjected to 75 min SMA clamp-induced ischemia follo wed by reperfusion and were killed at 0 min, 30 min, and 24 hr. Whole mount s of the jejunum were used to immunohistochemically quantify alterations in leukocytes, and circular muscle strips were used to assess organ bath musc le function. Muscularis and mucosa extracts were isolated from the intestin e and used for reverse transcription assisted polymerase chain reaction mRN A 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 n eutrophils and monocytes into the intestinal muscularis and a functional su ppression in jejunal circular muscle contractions. These UR injury induced cellular responses were preceded by the molecular activation of nuclear fac tor kappa B, upregulation of granulocyte colony-stimulating factor and inte rleukin-6 mRNA and phosphorylation of the downstream signaling and transcri ption factor Stat3. Conclusions. I/R injury evokes a molecular and cellular inflammatory respon se within the intestinal muscularis that is associated with a subsequent de crease in intestinal motility.