Abstract
Background. Excisional wound healing in inducible nitric oxide synthase knockout (iNOS-KO) mice
has been previously shown to be impaired compared with their background strain controls.
Incisional wounds were created in this experiment in both types of animals and paradoxically
were found to heal with the same rapidity and breaking strength in both groups. Methods. Dorsal 2.5 cm incisional wounds were created in iNOS-KO mice, as well as their parental
strain controls (C57BL/6J). Standardized polyvinyl alcohol sponges were implanted
in the wounds to allow for measurement of collagen deposition. Animals were harvested
on postoperative days (PODs) 3, 5, 7, 10, 14, and 28, and their wounds subjected to
tensiometric breaking strength analysis. Nonisotopic in situ hybridization quantitative
analysis for iNOS, endothelial NOS (eNOS), basic fibroblast growth factor (bFGF),
transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF),
and interleukin-4 (IL-4) expression in the wounds was performed. Hydroxyproline levels
were quantitated in the harvested polyvinyl alcohol sponges. Data were analyzed with
the Students t test. Results. No significant differences were found in breaking strengths or levels of hydroxyproline
(and thus collagen) in iNOS-KO versus wild-type wounds at all tested time points.
Flawed iNOS expression levels in iNOS-KO animals were similar to (functional) iNOS
expression in wild-types. eNOS and bFGF expression nearly doubled on POD 7 in iNOS-KO
incisions (P =.002, and.002), respectively and remained 200% to 300% elevated thereafter.
TGF-β1 expression was increased approximately 50% to 100% in iNOS-KO wounds on PODs
5 and 7 (P =.006 and.01, respectively). VEGF and IL-4 expression was elevated by 25%
to 100% in wild-type compared with iNOS-KO animals at all time points (P <.01). Conclusions. The overexpression of TGF-β1 and eNOS may represent mechanisms in iNOS-KO mice to
compensate for their loss of functional iNOS, resulting in incisional wound healing
equivalent to controls. Their impaired expression of VEGF and IL-4, on the other hand,
may partially explain the delayed excisional wound healing noted in these animals.
(Surgery 2002;132:866-76.)
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Article info
Publication history
Accepted:
May 31,
2002
Footnotes
*Supported by grant # GM54566 (A.B.) from the National Institutes of Health.
**Reprint requests: A.B. Surgeon-in-Chief, Department of Surgery, The Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215.
Identification
Copyright
© 2002 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
