Adhesions following abdominal surgery remain a significant unresolved clinical problem causing a great deal of post-operative morbidity. To date adhesion prevention strategies have proven of limited effectiveness. Osteopontin COPN) is a cytokine up-regulated in cell injury and tissue repair. Previous studies have shown that blocking OPN expression in the cutaneous wound demonstrates reduced granulation tissue and scarring without compromising healing. I hypothesise that it might be possible to produce a similar effect on inflammation associated fibrosis that leads to inter-loop bowel adhesions after intra-peritoneal surgery using a murine model. My experimental work on OPN suppression using mRNA blockade by delivering OPN antisense oligodeoxynucleotides on to the surface of injured juxtaposed small bowel supports this hypothesis. There was a significant reduction in granulation tissue and subsequent adhesion size. Also demonstrated was a significant reduction of leukocyte flux, alpha smooth muscle actin expression and collagen density within developing adhesions. There was no impact on mortality or delay in wound healing. Inflammation triggered by expression of OPN was not essential for healing of serosal injury to bowel within the peritoneal cavity. Blocking OPN expression is a very interesting target for anti-adhesion therapeutics.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:573930 |
| Date | January 2012 |
| Creators | Andrews, Stuart |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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