The effect of subcutaneous unfractionated heparin and low-molecular weight heparin toward modification of diabetic acute influence on surgical wound healing in rats


1 Department of General Surgery, Kashan University of Medical Sciences, Isfahan, Iran

2 Department of Clinical Pathology, Kashan University of Medical Sciences, Isfahan, Iran

3 Department of Physiology, Kashan University of Medical Sciences, Isfahan, Iran

4 Epidemiology, School of Medicine, Kashan University of Medical Sciences, Isfahan, Iran

5 Department of General Surgery, Isfahan University of Medical Sciences, Isfahan, Iran


Background and Objectives: Diabetes mellitus is one of the disturbing factors in surgical wound repair that recognizing these mechanisms, and modifying them can be useful in preventing surgical wound complications. The aim of this study is to assess the effect of unfractionated heparin (UH) and low-molecular weight heparin (LMWH) on diabetic wounds in the rats. Materials and Methods: This study as a clinical trial in the animal phase was done in two groups that each group consists of three subgroups containing eight rats in each. Initially, under anesthesia, the skin was incised surgically, and interventions with UH in the first subgroup of each group, LMWH in the second subgroup, and normal saline in the third subgroup were performed. In the first group on the 7th day and the second group on the 10th day, wound biopsy was taken and examined pathologically. Finally, data were analyzed using Kruskal–Wallis and one-way analysis of variance statically test. Results: The results of this study showed in every two groups, there was a statistically significant difference between the subgroups for fibroblast and vascularity status, but this difference was not significant for epithelialization and collagen level. In addition, wound length in both the groups had a significant difference between subgroups. Conclusion: In this study, there was a relative difference between the administration of UH and low-molecular weight and surgical wound healing in diabetic rats.


1. Gonzalez AC, Costa TF, Andrade ZD, Medrado AR. Wound healing – A literature review. An Bras Dermatol 2016;91:614‑20.
2. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res 2010;89:219‑29.
3. Katsuhiro M, Hui Teoh S, Yamashiro H, Shinohara M, Fatchiyah F, Ohta T, et al. Effects on glycemic control in impaired wound healing in spontaneously diabetic torii (SDT) fatty rats. Med Arch 2018;72:4‑8.
4. Yuan Y, Das SK, Li M. Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic mice by suppressing NF-κB-mediated inflammatory genes. Biosci Rep 2018;38.
5. Freudenberg U, Zieris A, Chwalek K, Tsurkan MV, Maitz MF, et al. Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds. J Control Release 2015;220:79‑88.
6. Salazar JJ, Ennis WJ, Koh TJ. Diabetes medications: Impact on inflammation and wound healing. J Diabetes Complications 2016;30:746‑52.
7. Martin P, Leibovich SJ. Inflammatory cells during wound repair: The good, the bad and the ugly. Trends Cell Biol 2005;15:599‑607.
8. Mirza R, DiPietro LA, Koh TJ. Selective and specific macrophage ablation is detrimental to wound healing in mice. Am J Pathol 2009;175:2454‑62.
9. Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Muller W, et al. Differential roles of macrophages in diverse phases of skin repair. J Immunol 2010;184:3964‑77.
10. Okonkwo UA, DiPietro LA. Diabetes and wound angiogenesis. Int J Mol Sci 2017;18:1419.
11. Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, et al. Epithelialization in wound healing: A Comprehensive review. Adv Wound Care (New Rochelle) 2014;3:445‑64.
12. Gibran NS, Jang YC, Isik FF, Greenhalgh DG, Greenhalgh DG, Muffley LA, et al. Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. J Surg Res 2002;108:122‑8.
13. Galiano RD, Tepper OM, Pelo CR, Pelo CR, Bhatt KA, Bhatt KA, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and  recruiting bone marrowderived cells. Am J Pathol 2004;164:1935‑47.
14. Eming SA, Martin P, Tomic‑Canic M. Wound repair and regeneration: Mechanisms, signaling, and translation. Sci Transl Med 2014;6:265sr6.
15. Oken OF, Yildirim AO, Gulcek M, Unal VS, Karakuyu A, Ozlu K, et al.The effect of prophylactic dose of a low molecular weight heparin on skin wound healing of rats. Acta Cir Bras 2009;24:471‑5.
16. Galvan L. Effects of heparin on wound healing. J Wound Ostomy Continence Nurs 1996;23:224‑6.
17. Black E, Vibe‑Petersen J, Jorgensen LN, Madsen SM, Agren MS, Holstein PE, et al. Decrease of collagen deposition in wound repair in type 1 diabetes independent of glycemic control. Arch Surg 2003;138:34‑40.
18. Civelek A, Ak K, Kurtkaya O, Tekeli A, Isbir S, Nargileci E, et al. Effect of a low molecular weight heparin molecule, dalteparin, on cellular apoptosis and inflammatory process in an incisional wound‑healing model. Surg Today 2007;37:406‑11.
19. Jörneskog G, Brismar K, Fagrell B. Low molecular weight heparin seems to improve local capillary circulation and healing of chronic foot ulcers in diabetic patients. Vasa 1993;22:137‑42.
20. Oturai PS. Effects of heparin on vascular dysfunction in diabetic rats. Clin Exp Pharmacol Physiol 1999;26:411‑4.
21. Kweon DK, Song SB, Park YY. Preparation of water‑soluble chitosan/heparin complex and its application as wound healing accelerator. Biomaterials 2003;24:1595‑601.
22. Durmaz CE, Ozkan A, Senel B, Uyar HA. Comparison of effects of unfractionated heparin and low molecular weight heparin on skin wound healing of rats. Acta Cir Bras 2012;27:639‑44