Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds

被引:92
作者
Buemi, M
Galeano, M
Sturiale, A
Ientile, R
Crisafulli, C
Parisi, A
Catania, MA
Calapai, G
Impalà, P
Aloisi, C
Squadrito, F
Altavilla, D
Bitto, A
Tuccari, G
Frisina, N
机构
[1] Univ Messina, Dept Internal Med, Sect Plast Surg, I-98100 Messina, Italy
[2] Univ Messina, Dept Surg Sci, Sect Plast Surg, I-98100 Messina, Italy
[3] Univ Messina, Dept Physiol, Biochem Sect, I-98100 Messina, Italy
[4] Univ Messina, Dept Pathol, Pharmacol Sect, I-98100 Messina, Italy
[5] Univ Messina, Dept Clin & Expt Med & Pharmacol, Pharmacol Sect, I-98100 Messina, Italy
来源
SHOCK | 2004年 / 22卷 / 02期
关键词
angiogenesis; erythropoietin; skin ischemia; tissue transglutaminase; VEGF;
D O I
10.1097/01.shk.0000133591.47776.bd
中图分类号
R4 [临床医学];
学科分类号
1002 [临床医学]; 100602 [中西医结合临床];
摘要
Wound healing in ischemic tissues such as flap margins due to inadequate blood supply is still a source of considerable morbidity in surgical practice. Adequate tissue perfusion is particularly important in wound healing. We investigated the effects of recombinant human erythropoietin (rHuEPO) on wound healing in an ischemic skin wound model. Sixty-three Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. Animals were treated with rHuEPO (400 IU/kg) or its vehicle. Rats were killed on different days (3, 5, and 10 days after skin injury) and the wounded skin tissues were used for immunohistochemistry and for analysis of vascular endothelial growth factor content and collagen content. Tissue transglutaminase immunostaining of histological specimens was used as a vascular marker to determine the level of microvessel density. The results showed a higher level of vascular endothelial growth factor protein and an increased microvessel density in ischemic wounds with rHuEPO treatment than the normal incisional wounds and ischemic control wounds. Collagen content was higher in the incisional wounds and in the ischemic wounds with rHuEPO treatment compared with the ischemic control wounds. Our results suggest that erythropoietin may be an effective therapeutic approach in improving healing in ischemic skin wounds.
引用
收藏
页码:169 / 173
页数:5
相关论文
共 33 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].
Altavilla, D ;
Saitta, A ;
Cucinotta, D ;
Galeano, M ;
Deodato, B ;
Colonna, M ;
Torre, V ;
Russo, G ;
Sardella, A ;
Urna, G ;
Campo, GM ;
Cavallari, V ;
Squadrito, G ;
Squadrito, F .
DIABETES, 2001, 50 (03) :667-674
[2]
Direct effect of erythropoietin on rat vascular smooth-muscle cell via a putative erythropoietin receptor [J].
Ammarguellat, F ;
Gogusev, J ;
Drueke, TB .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 1996, 11 (04) :687-692
[3]
ERYTHROPOIETIN HAS A MITOGENIC AND POSITIVE CHEMOTACTIC EFFECT ON ENDOTHELIAL-CELLS [J].
ANAGNOSTOU, A ;
LEE, ES ;
KESSIMIAN, N ;
LEVINSON, R ;
STEINER, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (15) :5978-5982
[4]
ANGIOGENESIS IN WOUND-HEALING [J].
ARNOLD, F ;
WEST, DC .
PHARMACOLOGY & THERAPEUTICS, 1991, 52 (03) :407-422
[5]
BIKFALVI A, 1994, LEUKEMIA, V8, P523
[6]
Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent -: A new paradigm in wound healing [J].
Brem, H ;
Balledux, J ;
Bloom, T ;
Kerstein, MD ;
Hollier, L .
ARCHIVES OF SURGERY, 2000, 135 (06) :627-634
[7]
EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) BY EPIDERMAL-KERATINOCYTES DURING WOUND-HEALING [J].
BROWN, LF ;
YEO, KT ;
BERSE, B ;
YEO, TK ;
SENGER, DR ;
DVORAK, HF ;
VANDEWATER, L .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (05) :1375-1379
[8]
Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps [J].
Buemi, M ;
Vaccaro, M ;
Sturiale, A ;
Galeano, MR ;
Sansotta, C ;
Cavallari, V ;
Floccari, F ;
D'Amico, D ;
Torre, V ;
Calapai, G ;
Frisina, N ;
Guarneri, F ;
Vermiglio, G .
ACTA DERMATO-VENEREOLOGICA, 2002, 82 (06) :411-417
[9]
Choi K, 1998, DEVELOPMENT, V125, P725