Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes

被引：132

作者：

Bitto, Alessandra ^{[1
]}

Minutoli, Letteria ^{[1
]}

Altavilla, Domenica ^{[1
]}

Polito, Francesca ^{[1
]}

Fiurnara, Tiziana ^{[1
]}

Marini, Herbert ^{[2
]}

Galeano, Mariarosaria ^{[3
]}

Calo, Margherita ^{[4
]}

Lo Cascio, Patrizia ^{[5
]}

Bonaiuto, Michele ^{[6
]}

Migliorato, Alba ^{[7
]}

Caputi, Achille P. ^{[1
]}

Squadrito, Francesco ^{[1
]}

机构：

[1] Univ Messina, Pharmacol Sect, Dept Expt & Clin Med & Pharmacol, I-98100 Messina, Italy

[2] Univ Messina, Sect Physiol & Human Nutr, Dept Biochem Physiol & Nutr Sci, I-98100 Messina, Italy

[3] Univ Messina, Sect Plast Surg, Dept Surg Sci, I-98100 Messina, Italy

[4] Univ Messina, Sect Vet Pharmacol & Toxicol, Dept Vet Publ Hlth, I-98100 Messina, Italy

[5] Univ Messina, Dept Anim Biol & Marine Ecol, I-98100 Messina, Italy

[6] Univ Messina, Dept Internal Med, I-98100 Messina, Italy

[7] Univ Messina, Dept Biomorphol & Biotechnol, I-98100 Messina, Italy

来源：

PHARMACOLOGICAL RESEARCH | 2008年 / 57卷 / 02期

关键词：

diabetes; PECAM-1; simvastatin; VEGF; wound healing;

D O I：

10.1016/j.phrs.2008.01.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Statins have different effects beyond cholesterol reduction and stimulate angiogenesis. We investigated the effect of simvastatin in diabetes-related healing defects. An incisional skin wound model produced on the back of female diabetic mice (db(+)/db(+)) and their normoglycemic littermates (db(+)/(+)m) was used. Animals were treated daily either with simvastatin (5 mg/(kg i.p.)) or vehicle. Mice were killed on different days (3, 6 and 12 after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA and protein expression, to assess histologically the healing process and to evaluate wound breaking strength and angiogenesis by CD31 immunostaining. Simvastatin administration in diabetic mice increased VEGF mRNA (simvastatin = 4.8 +/- 0.6 n-fold/beta-actin; vehicle = 2.3 +/- 0.4 n-fold/beta-actin) and protein expression (simvastatin = 5 +/- 0.7 integrated intensity; vehicle = 2.2 +/- 0.3 integrated intensity) and enhanced nitric oxide wound content at day 6. Additionally, the statin augmented breaking strength and PECAM-1 immunostaining at day 12. Finally, simvastatin administration restored the impaired wound healing process in diabetic mice. Similar results were obtained in normoglycaemic mice. Passive immunization with anti-VEGF antibody (10 mu g/mouse) completely abrogated the beneficial effects of simvastatin on healing in diabetic mice. Simvastatin has potential application in diabetes-related wound healing disorders. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：159 / 169

页数：11

共 32 条

[1] Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse [J].