title: Use of insulin-like growth factor in the healing of open wounds in diabetic and non-diabetic rats.
abstract: OBJECTIVE
  To analyze the effects of application of 1% and 3% insulin-like growth factor I (IGF-1) cream on the process of wound healing in induced skin lesions in diabetic and non-diabetic rats and evaluate its effect on expression of myofibroblasts.
  
  
  METHODS
  Ninety-six Wistar adult male rats were divided into six groups, with 16 rats in each group, as follows: group 1: non-diabetic, untreated; group 2: non-diabetic, treated with 1% IGF-1 cream; group 3: non-diabetic, treated with 3% IGF-1 cream; group 4: diabetic, untreated; group 5: diabetic, treated with 1% IGF-1 cream; and group 6: diabetic, treated with 3% IGF-1 cream. In groups 4, 5, and 6, diabetes was induced by intravenous injection of alloxan. After diabetes had been induced, animals were mantained for 3 months. The experimental procedure consisted of the creation of a circular incision of 0.9 mm in diameter using a metal punch. Following this, wounds were treated daily according to the assigned treatment regimen. Groups 2 and 5 were treated with 1% IGF-1 cream, groups 3 and 6 with 3% IGF-1 cream, and groups 1 and 4 and the untreated groups with 0.9% saline solution. From each group, samples from 4 rats were taken at three, seven, 14, and 21 days after the injury. Samples were fixed in 10% formalin to prepare slides for histological analysis. Slides stained with hematoxylin-eosin (H&E) and Masson were observed vascular proliferation, mononuclear cells, polymorphonuclear cells, fibroblast proliferation, re-epithelialization, and collagen fibers. This study analyzed the expression of α-smooth muscle actin using specific antibodies to correlate the temporal expression of α-smooth muscle-specific actin (α-SM actin), a molecular marker for myofibroblast transformation.
  
  
  RESULTS
  Macroscopic observation of wounds showed a more rapid re-epithelialization of wounds treated with IGF. Regarding acute inflammatory reactions, the results of the analysis of vascular proliferation and polymorphonuclear and mononuclear cells showed no statistically significant differences in any of the periods studied (according to the results of a Mann-Whitney test). The initial immunohistochemical analysis of tissue samples conducted to compare the expression of α-smooth muscle actin between groups showed a relevant response in the expression of myofibroblasts. Data were analyzed using ANOVA and were found to be statistically significant.
  
  
  CONCLUSIONS
  The topical application of 1% and 3% IGF-1 creams increases the expression of myofibroblasts in the process of wound healing in rats.
authors.affiliation: Sao Paulo City University, Sao PauloSP, Brazil, Fellow Master degree, Postgraduate Program in Health Sciences, Sao Paulo State Public Servant Hospital (IAMSPE). Associate Professor, Experimental Surgery, Sao Paulo City University (UNICID), Sao Paulo-SP, Brazil. Conception, design, scientific and intellectual content of the study; manuscript writing.
authors.forename: Rosi Aparecida Nunes
authors.initials: RA
authors.lastname: Achar
authors.affiliation: UNICID, Medical School, Sao PauloSP, Brazil, Graduate student, Medical School, UNICID, Grant from Institutional Program for Scientific Initiation (PIBIC) of the National Council of Technological and Scientific Development (CNPq), Ministry of Science, Technology and Inovation, Sao Paulo-SP, Brazil. Acquisition of data, technical procedures.
authors.forename: Thiago Couto
authors.initials: TC
authors.lastname: Silva
authors.affiliation: UNICID, Sao PauloSP, Brazil, PhD, Associate Professor, Experimental Surgery, UNICID, Sao Paulo-SP, Brazil. Technical procedures, critical revision.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Achar
authors.affiliation: Adolfo Lutz Institute, Sao PauloSP, Brazil, PhD, Medical Pathologist, Adolfo Lutz Institute, Sao Paulo-SP, Brazil. Histological analysis.
authors.forename: Roosecelis Brasil
authors.initials: RB
authors.lastname: Martines
authors.affiliation: UNICID, Sao PauloSP, Brazil, PhD, Associate Professor, Postgraduate Program in Health Sciences, IAMSPE. Associate Professor, Experimental Surgery, UNICID, Sao Paulo-SP, Brazil. Manuscript writing, supervised all phases of the study.
authors.forename: José Lucio Martins
authors.initials: JL
authors.lastname: Machado
mesh_terms: D000199:Actins / Q000032:analysis; D000287:Administration, Topical; D000496:Alloxan; D000818:Animals; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects*; D017208:Rats, Wistar; D015203:Reproducibility of Results; D063465:Skin Cream / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000199:Actins; C544013:alpha-smooth muscle actin, mouse; D007334:Insulin-Like Growth Factor I; D000496:Alloxan