title: Zucker diabetic fatty rat: a new model of impaired cutaneous wound repair with type II diabetes mellitus and obesity.
abstract: Impaired diabetic wound healing is an important current medical issue, mainly concerning patients recovering from complicated operations or patients with ulcers on their feet. The obese Zucker diabetic fatty rat, with a mutation in leptin receptors, may be a good choice for studying impaired wound healing. Male and female rats were fed a diabetogenic high-fat diet. Wound size changes of air-exposed excisional 2 cm circular wounds were measured until Day 10. Wound tissue was analyzed morphologically, histologically, and immunohistochemically. The hydroxyproline content in the granulation tissue (GT) was determined. mRNA expression was assayed by DNA-array analysis and real-time reverse transcription-polymerase chain reaction. Wound-size changes were retarded in diabetic rats and differed between the sexes. Diabetic wounds were characterized by impaired contraction, abundant crust production, increased inflammation, and pus formation. On Day 10, the GT contained a significantly increased amount of intercalated fat tissue and showed an irregular arrangement of GT and collagen fibers. Interestingly, the length of new epithelium was increased in diabetic wounds. The concentration of hydroxyproline in the GT of diabetic animals was significantly decreased to about one half when compared with the nondiabetic controls. The expression of interleukin-6, myeloperoxidase, stromelysin-1, and collagenase-3 was increased in the GT of diabetic rats on Day 10, while the expression of type I collagen and elastin was decreased. Taken together, Zucker diabetic fatty rats exhibited impairments in wound-size reduction, inflammatory response, tissue organization, and connective tissue turnover and are thus proposed as a new model for studying impaired repair.
authors.affiliation: Laboratory of Wound Healing, CPN, Dolni Dobrouc, Czech Republic. rastik@gmail.com
authors.forename: Rastislav
authors.initials: R
authors.lastname: Slavkovsky
authors.forename: Renata
authors.initials: R
authors.lastname: Kohlerova
authors.forename: Vlasta
authors.initials: V
authors.lastname: Tkacova
authors.forename: Alena
authors.initials: A
authors.lastname: Jiroutova
authors.forename: Burak
authors.initials: B
authors.lastname: Tahmazoglu
authors.forename: Vladimir
authors.initials: V
authors.lastname: Velebny
authors.forename: Martina
authors.initials: M
authors.lastname: Rezačová
authors.forename: Lubos
authors.initials: L
authors.lastname: Sobotka
authors.forename: Jiri
authors.initials: J
authors.lastname: Kanta
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D005260:Female; D006097:Granulation Tissue / Q000378:metabolism / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D012737:Sex Factors; D012867:Skin / Q000293:injuries* / Q000473:pathology; D013492:Suppuration / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D015850:Interleukin-6; D004549:Elastin; D009195:Peroxidase; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D006909:Hydroxyproline