title: Nitric oxide restores impaired healing in normoglycaemic diabetic rats.
abstract: OBJECTIVE
  Hyperglycaemia impairs wound healing. However, little is known about the underlying cellular mechanisms that lead to diminished wound repair in insulin-controlled and non-insulin-controlled diabetes. This study investigated the role of endogenous and exogenous nitric oxide on incisional wound healing in diabetic rats.
  
  
  METHODS
  Groups of 10 wild-typeWistar control rats - 10 genetically diabetic BioBreeding rats and 10 genetically diabetic BioBreeding rats treated with subcutaneous insulin implants to render them normoglycaemic - underwent dorsal skin incision followed by subcutaneous insertion of polyvinyl alcohol sponges. The rats were sacrificed 10 days later to determine the wound-breaking strength and reparative collagen deposition. Nitric oxide, an important mediator in diabetic wound healing and collagen synthesis, was measured in wound fluid. Wound-derived fibroblasts were tested for ex vivo synthesis of nitric oxide and collagen. Exogenous nitric oxide was used for the therapeutic interventions.
  
  
  RESULTS
  Wound-breaking strength and wound collagen deposition were significantly impaired in the hyperglycaemic diabetic animals (p<0.01). Wound nitric-oxide synthesis and ex vivo wound fibroblast nitric-oxide production were reduced in the hyperglycaemic rats (p<0.01). Insulin treatment partially reversed some of the effects of hyperglycaemia on wound repair (p<0.05). Exogenous nitric oxide further restored wound mechanical strength, collagen deposition and fibroblast collagen synthesis (p<0.01) in insulin-treated (normoglycaemic) diabetic animals.
  
  
  CONCLUSIONS
  Wound healing is impaired in hyperglycaemic and normoglycaemic diabetic rats. This is reflected in impaired wound fibroblast nitric-oxide synthesis. Used in combination with insulin, exogenous nitric oxide further improves healing outcomes, making it a potential target for therapeutic intervention in insulin-treated normoglycaemic diabetes.
authors: I Department of Surgery, University Hospital, Knappschaftskrankenhaus Bochum-Langendreer, Germany. michael.schaeffer@kk-bochum.de
authors: M
authors: M
authors: Schäffer
authors: M
authors: M
authors: Bongartz
authors: S
authors: S
authors: Fischer
authors: B
authors: B
authors: Proksch
authors: R
authors: R
authors: Viebahn
mesh_terms: D000818:Animals; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011922:Rats, Mutant Strains; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D016166:Free Radical Scavengers; D009569:Nitric Oxide; D003094:Collagen