Expression of neuropeptides and cytokines in a rabbit model of diabetic neuroischemic wound healing.
J Vasc Surg
; 58(3): 766-75.e12, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23755976
ABSTRACT
OBJECTIVE:
The present study is designed to understand the contribution of peripheral vascular disease and peripheral neuropathy to the wound-healing impairment associated with diabetes. Using a rabbit model of diabetic neuroischemic wound healing, we investigated rate of healing, leukocyte infiltration, and expression of cytokines, interleukin-8 and interleukin-6, and neuropeptides, substance P, and neuropeptide Y.METHODS:
Diabetes was induced in New Zealand White rabbits by administering alloxan while control rabbits received saline. Ten days later, animals in both groups underwent surgery. One ear served as a sham, and the other was made ischemic (ligation of central+rostral arteries) or neuroischemic (ischemia+ resection of central+rostral nerves). Four 6-mm punch biopsy wounds were created in both ears and wound healing was followed for 10 days using computerized planimetry.RESULTS:
Nondiabetic sham and ischemic wounds healed significantly more rapidly than diabetic sham and ischemic wounds. Healing was slowest in neuroischemic wounds, irrespective of diabetic status. A high M1/M2 macrophage ratio and a high proinflammatory cytokine expression, both indicators of chronic proinflammatory state, and low neuropeptide expression were seen in preinjury diabetic skin. Postinjury, in diabetic wounds, the M1/M2 ratio remained high, the reactive increase in cytokine expression was low, and neuropeptide expression was further decreased in neuroischemic wounds.CONCLUSIONS:
This rabbit model illustrates how a combination of a high M1/M2 ratio, a failure to mount postinjury cytokine response as well as a diminished neuropeptide expression, contribute to wound-healing impairment in diabetes. The addition of neuropathy to ischemia leads to equivalently severe impaired wound-healing irrespective of diabetes status, suggesting that in the presence of ischemia, loss of neuropeptide function contributes to the impaired healing associated with diabetes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Úlcera Cutânea
/
Cicatrização
/
Neuropeptídeos
/
Citocinas
/
Mediadores da Inflamação
/
Diabetes Mellitus Experimental
/
Angiopatias Diabéticas
/
Neuropatias Diabéticas
/
Isquemia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Vasc Surg
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos