Effect of atorvastatin on wound healing in rats

Biol Res Nurs. 2015 Mar;17(2):159-68. doi: 10.1177/1099800414537348. Epub 2014 Jun 12.

Abstract

Skin-wound healing is a complex and dynamic biological process involving inflammation, proliferation, and remodeling. Recent studies have shown that statins are new therapeutical options because of their actions, such as anti-inflammatory and antioxidant activity, on vasodilation, endothelial dysfunction and neoangiogenesis, which are independent of their lipid-lowering action. Our aim was to investigate the effect of atorvastatin on tissue repair after acute injury in healthy animals. Rats were divided into four groups: placebo-treated (P), topical atorvastatin-treated (AT), oral atorvastatin-treated (AO), topical and oral atorvastatin-treated (ATO). Under anesthesia, rats were wounded with an 8-mm punch in the dorsal region. Lesions were photographed on Days 0, 1, 3, 7, 10, 12, and 14 post-injury and samples taken on Days 1, 3, 7, and 14 for protein-expression analysis of insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase (GSK)-3, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK), interleukin (IL)-10, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. Upon macroscopic examination, we observed significant reductions of lesion areas in groups AT, AO, and ATO compared to the P group. Additionally, AT and AO groups showed increased expression of IRS-1, PI3K, Akt, GSK-3, and IL-10 on Days 1 and 3 when compared with the P group. All atorvastatin-treated groups showed higher expression of IRS-1, PI3K, Akt, GSK-3, IL-10, eNOS, VEGF, and ERK on Day 7. On Days 1, 3, and 7, all atorvastatin-treated groups showed lower expression of IL-6 and TNF-α when compared with the P group. We conclude that atorvastatin accelerated tissue repair of acute lesions in rats and modulated expressions of proteins and cytokines associated with cell-growth pathways.

Keywords: hydroxymethylglutaryl-CoA reductase inhibitors; nursing; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Animals
  • Atorvastatin / administration & dosage
  • Atorvastatin / pharmacology*
  • Extracellular Signal-Regulated MAP Kinases / analysis
  • Glycogen Synthase Kinase 3 / analysis
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Immunoblotting
  • Interleukin-10 / analysis
  • Interleukin-1beta / analysis
  • Interleukin-6 / analysis
  • Male
  • Nitric Oxide Synthase Type III / analysis
  • Peptide Fragments / analysis
  • Phosphatidylinositol 3-Kinase / analysis
  • Proto-Oncogene Proteins c-akt / analysis
  • Rats
  • Receptor, Insulin / analysis
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Endothelial Growth Factor A / analysis
  • Wound Healing / drug effects*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-1beta
  • Interleukin-6
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • interleukin-1beta (163-171)
  • Interleukin-10
  • Atorvastatin
  • Nitric Oxide Synthase Type III
  • Phosphatidylinositol 3-Kinase
  • Receptor, Insulin
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Glycogen Synthase Kinase 3