ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 27 of 32
УЖМБС 2022, 7(6): 182–187

Histological Characteristics of Experimental Wounds of Soft Tissues of the Femur of Rats and the Role of IFN-γ in the Dynamics of their Healing

Ionov I. A., Komisova T. Ye.

The purpose of the study was to evaluate the histomorphological changes in samples of the wound canal of the soft tissues of the femur of rats and to study the role of interferon-gamma (IFN-γ) in the dynamics of wound healing. Materials and methods. The study was conducted on 24 Wistar rats. Animals were divided into two groups – intact (6 rats) and experimental (18 rats). Animals of the experimental group were used to simulate wounds. Rats were euthanized on the 10th, 20th, and 40th days (6 animals for each time) after wound simulation. Blood for the study was taken by the method of open cardiac puncture. The levels of INF-γ in the blood serum of animals were determined by enzyme immunoassay. Histological processing of the samples was carried out according to generally accepted methods, the sections were stained with hematoxylin and eosin, as well as picrofuchsin according to Van Gieson. Results and discussion. The work revealed changes in the expression of IFN-γ in the blood serum of animals with wounds: an increase in the levels of IFN-γ on the 10th and 20th days after modeling wounds compared to the levels of rats in the intact group (p<0.05). A decrease in the levels of IFN-γ on the 40th day of the experiment compared to a similar level of this cytokine on the 10th and 20th days after wound simulation was shown (p<0.05). The results of histological studies show signs of the proliferative phase in the form of a significant number of fibroblasts and newly formed vessels, as well as the beginning of the remodeling stage in the form of the organization of collagen fibers in parallel bundles in the wound canals in different areas within 10 days. On the 20th day, the absence of inflammatory cells in the preparations of the damaged areas is noted. Also at the tissue level at this time, signs of the remodeling phase were revealed: a significant decrease in the number of blood vessels and fibroblasts was observed, the connective tissue in the areas acquired a mature appearance in the form of dense layers with single fibrocytes. In the injury zone on the 40th day of the experiment, scars from mature connective tissue were noted. Conclusion. In an experimental study, we showed the morphological and physiological features of the healing of soft tissue injuries in normal rats. The established structural features of wound areas at different stages of healing and the dynamics of IFN-γ release allow us to determine its important role not only in inflammation, but also in the stages of proliferation and remodeling. Determination of the concentration of IFN-γ may be an informative indicator at all stages of repair in the process of healing soft tissue injuries in humans, subjected to further clinical studies

Keywords: cytokine, repair, inflammation, wound healing, histological studies

Full text: PDF (Ukr) 388K

  1. Abebe T, Boru Y, Belay E, Abebe A, Kefyalew M, Kifle F. Clinical profile and outcomes of trauma patients visiting the emergency department of a trauma center Addis Ababa, Ethiopia. African journal of emergency medicine: Afr J Emerg Med. 2022 Dec;12(4):478-483. PMID: 36419758 PMCID: PMC9676199. doi: 10.1016/j.afjem.2022.10.013
  2. Krishtafor DA, Klygunenko OM, Krishtafor AA. Comparative characteristics of civilian and military multiple trauma in a level III hospital. Emerg Med. 2019;3(98):127-33.
  3. Lurin IA, Khomenko IP, Gumeniuk KV, Korol SO, Tsema IV, Tertyshnyi SV, Popova OМ. Features of the key type and character of fire injuries of military personnel during modern armed conflicts. Kharkiv surgical school.  2022;2(113):59-63. doi: 10.37699/2308-7005.2.2022.12
  4. Schlager JG, Hartmann D, Wallmichrath J, San Jose VR, Patzer K, French LE, et al. Patient-dependent risk factors for wound infection after skin surgery: A systematic review and meta-analysis. Int Wound J. 2022;19(7):1748-57. PMID: 35229471. PMCID: PMC9615300. doi: 10.1111/iwj.13780
  5. Kanikovskyi OE, Bondarchuk OI, Sander SV, Kroshka VM, Lopushanskyi OM. Severity and prognosis assessment criteria for purulent-inflammatory diseases. Kharkiv surgical school. 2022; 1(113):37-40. doi: 10.37699/2308-7005.2.2022.07
  6. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound Healing: A Cellular Perspective. Physiol Rev. 2019;99(1):665-706. PMID: 30475656. PMCID: PMC6442927. doi: 10.1152/physrev.00067.2017
  7. Larouche J, Sheoran S, Maruyama K, Martino MM. Immune Regulation of Skin Wound Healing: Mechanisms and Novel Therapeutic Targets. Adv Wound Care (New Rochelle). 2018 Jul 1;7(7):209-231. PMID: 29984112. PMCID: PMC6032665. doi: 10.1089/wound.2017.0761
  8. Chen Y, Tian B. IFN-γ promotes the development of systemic lupus erythematosus through the IFNGR1/2-PSTAT1-TBX21 signaling axis. Am J Transl Res. 2022; 14(10):6874-88.
  9. Kanno E, Tanno H, Masaki A, Sasaki A, Sato N, Goto M, et al. Defect of Interferon-γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation. Int J Mol Sci. 2019;20(22):5657. PMID: 31726690. PMCID: PMC6888635. doi: 10.3390/ijms20225657
  10. Holt V, Morén B, Fryklund C, Colbert RA, Stenkula KG. Acute cytokine treatment stimulates glucose uptake and glycolysis in human keratinocytes. Cytokine. 2023;161:156057. PMID: 36208532. doi: 10.1016/j.cyto.2022.156057
  11. Murata K, Murao A, Aziz M, Wang P. Extracellular CIRP Induces Novel Nectin-2+ (CD112+) Neutrophils to Promote Th1 Differentiation in Sepsis. J Immunol. 2022:ji2200308. PMID: 36480269. doi: 10.4049/jimmunol.2200308
  12. Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007;127(3):514-25. PMID: 17299434. doi: 10.1038/sj.jid.5700701
  13. Hamidzadeh K, Christensen SM, Dalby E, Chandrasekaran P, Mosser DM. Macrophages and the Recovery from Acute and Chronic Inflammation. Annu Rev Physiol. 2017 Feb 10;79:567-592. PMID: 27959619. PMCID: PMC5912892. doi: 10.1146/annurev-physiol-022516-034348
  14. Viera MH, Vivas AC, Berman B. Update on Keloid management: clinical and basic science advances. Adv Wound Care (New Rochelle). 2012 Oct;1(5):200-206. PMID: 24527306. PMCID: PMC3839006. doi: 10.1089/wound.2011.0313
  15. Janakiram NB, Valerio MS, Goldman SM, Dearth CL. The Role of the Inflammatory Response in Mediating Functional Recovery Following Composite Tissue Injuries. Int J Mol Sci. 2021;22(24):13552. PMID: 34948349. PMCID: PMC8705789. doi: 10.3390/ijms222413552
  16. Song J, Hu L, Liu B, Jiang N, Huang H, Luo J, et al. The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing. J Inflamm Res. 2022;15:4119-38. PMID: 35898820. PMCID: PMC9309318. doi: 10.2147/JIR.S371939
  17. Estep BK, Kuhlmann CJ, Osuka S, Suryavanshi GW, Nagaoka-Kamata Y, Samuel CN, et al. Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic. iScience. 2022; 25(12): 105544. PMID: 36406860. PMCID: PMC9650991. doi: 10.1016/j.isci.2022.105544
  18. Hsu A, Huntington KE, De Souza A, Zhou L, Olszewski AJ, Makwana NP, et al. Clinical activity of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, in refractory adult T-Cell leukemia/lymphoma. Cancer Biol Ther. 2022;23(1):417-23. PMID: 35815408. PMCID: PMC9272832. doi: 10.1080/15384047.2022.2088984
  19. Jin Q, Yao Z, Liu F, Di Y, Gao J, Zhang X. The protective effect of a combination of human intracellular and extracellular antibodies against the highly pathogenic avian influenza H5N1 virus. Hum Vaccin Immunother. 2022;18(1):2035118. PMID: 35240918. PMCID: PMC9009906. doi: 10.1080/21645515.2022.2035118
  20. Ding H, Wang G, Yu Z, Sun H, Wang L. Role of interferon-gamma (IFN-γ) and IFN-γ receptor 1/2 (IFNγR1/2) in regulation of immunity, infection, and cancer development: IFN-γ-dependent or independent pathway. Biomed Pharmacother. 2022;155:113683. PMID: 36095965. doi: 10.1016/j.biopha.2022.113683
  21. Steen-Louws C, Hartgring SAY, Popov-Celeketic J, Lopes AP, de Smet MBM, Eijkelkamp N, et al. IL4-10 fusion protein: a novel immunoregulatory drug combining activities of interleukin-4 and interleukin-10. Clin Exp Immunol. 2019;195(1):1-9. PMID: 30307604. PMCID: PMC6300648. doi: 10.1111/cei.13224