Low-intensity treadmill exercise promotes rat dorsal wound healing

Abstract

In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group (Ex) and non-exercise group (non-ex). The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two-week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells (EPCs) by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the mRNA level of VEGFR2 and angiopoietin-1 (Ang-1) receptor using RT-qPCR, and protein expression of a-smooth muscle actin (αSMA) and type III collagen (ColIII) using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, eNOS and bFGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the mRNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of αSMA and ColIII was more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound.

Keywords

wound healing / endothelial progenitor cells / treadmill exercise / vascular endothelial growth factor / angiopoietin

References

[1] CaiadoF, CarvalhoT, SilvaF, et al. . The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing. Biomaterials, 2011, 32(29): 7096-7105 PMID: 21741704

[2] SuhW, KimKL, KimJM, et al. . Transplantation of endothelial progenitor cells accelerates dermal wound healing with increased recruitment of monocytes/macrophages and neovascularization. Stem Cells, 2005, 23(10): 1571-1578 PMID: 16081667

[3] WooKY, BotrosM, KuhnkeJ, et al. . Best practices for the management of foot ulcers in people with diabetes. Adv Skin Wound Care, 2013, 26(11): 512-524 PMID: 24149666

[4] ForsbergJ, PotterB, CiernyGR, et al. . Diagnosis and management of chronic infection. J Am Acad Orthop Surg, 20111-8

[5] PenceBD, DipietroLA, WoodsJA. Exercise speeds cutaneous wound healing in high-fat diet-induced obese mice. Med Sci Sports Exerc, 2012, 44(10): 1846-1854 PMID: 22543735

[6] KeylockKT, VieiraVJ, WalligMA, et al. . Exercise accelerates cutaneous wound healing and decreases wound inflammation in aged mice. Am J Physiol Regul Integr Comp Physiol, 2007, 294(1): R179-R184 PMID: 18003791

[7] GuoS, YuL, ChengY, et al. . PDGFRbeta triggered by bFGF promotes the proliferation and migration of endothelial progenitor cells via p-ERK signalling. Cell Biol Int, 2012, 36(10): 945-950 PMID: 22731705

[8] Grochot-PrzeczekA, DulakJ, JozkowiczA. Therapeutic angiogenesis for revascularization in peripheral artery disease. Gene, 2013, 525(2): 220-228 PMID: 23566831

[9] SteinerS, NiessnerA, ZieglerS, et al. . Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease. Atherosclerosis, 2005, 181(2): 305-310 PMID: 16039284

[10] RehmanJ, LiJ, ParvathaneniL, et al. . Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. J Am Coll Cardiol, 2004, 43(12): 2314-2318 PMID: 15193699

[11] TokudaS, KaiM, KawaharaS, et al. . Changes in carbonic anhydrase activity in rat skeletal muscles due to aerobic treadmill exercise. J Sports Med Phys Fitness, 1987, 27(3): 380-384 PMID: 3123800

[12] BaiH, ForresterJV, ZhaoM. DC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptors. Cytokine, 2011, 55(1): 110-115 PMCID: 4437767 PMID: 21524919

[13] ShahraraS, VolinMV, ConnorsMA, et al. . Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Arthritis Res, 2002, 4(3): 201-208 PMCID: 111023 PMID: 12010571

[14] WilgusTA, MatthiesAM, RadekKA, et al. . Novel function for vascular endothelial growth factor receptor-1 on epidermal keratinocytes. Am J Pathol, 2005, 167(5): 1257-1266 PMCID: 1603795 PMID: 16251410

[15] FengY, YangS, XiaoB, et al. . Decreased in the number and function of circulation endothelial progenitor cells in patients with avascular necrosis of the femoral head. Bone, 2010, 46(1): 32-40 PMID: 19747991

[16] GuiC, LiSK, NongQL, et al. . Changes of serum angiogenic factors concentrations in patients with diabetes and unstable angina pectoris. Cardiovasc Diabetol, 2013, 12: 34 PMCID: 3598554 PMID: 23421785

[17] WangXH, ChenSF, JinHM, et al. . Differential analyses of angiogenesis and expression of growth factors in micro-and macrovascular endothelial cells of type 2 diabetic rats. Life Sci, 2009, 84(7–8): 240-249 PMID: 19135459

[18] LosiP, BrigantiE, ErricoC, et al. . Fibrin-based scaffold incorporating VEGF-and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice. Acta Biomater, 2013, 9(8): 7814-7821 PMID: 23603001

[19] TangX, YangY, YuanH, et al. . Novel transcriptional regulation of VEGF in inflammatory processes. J Cell Mol Med, 2013, 17(3): 386-397 PMCID: 3612137 PMID: 23414097

[20] Van SlykeP, AlamiJ, MartinD, et al. . Acceleration of diabetic wound healing by an angiopoietin peptide mimetic. Tissue Eng Part A, 2009, 15(6): 1269-1280 PMID: 18939935

[21] KaoHK, ChenB, MurphyGF, et al. . Peripheral blood fibrocytes: enhancement of wound healing by cell proliferation, re-epithelialization, contraction, and angiogenesis. Ann Surg, 2011, 254(6): 1066-1074 PMID: 21832942

[22] ChoiW, KawanabeH, SawaY, et al. . Effects of bFGF on suppression of collagen type I accumulation and scar tissue formation during wound healing after mucoperiosteal denudation of rat palate. Acta Odontol Scand, 2008, 66(1): 31-37 PMID: 18320416