online ISSN 2415-3176
print ISSN 1609-6371
logoЕкспериментальна та клінічна фізіологія і біохімія
Ж. 2026, 105(1): 50–58
https://doi.org/10.25040/ecpb2026.01.050

Експериментальна медицина


Концентрація факторів росту в рановому ложі при загоєнні повношарових вирізанних лінійних ран самців і самок щурів із глутамат-індукованим ожирінням

Н. Р. ГРИЦЕВИЧ1 , Н. С. НІКІТІНА2 , Л. І. СТЕПАНОВА2 , В. В. ВЕРЕЩАКА2 , О. М. САВЧУК2

Дата першого надходження: 27-01-2026

Дата прийняття до друку: 25-03-2026

Опубліковано: 03-05-2026

Анотація

Abstract. The healing process of minor acute wounds is mainly facilitated by the skin's inherent regenerative capacity, which includes cellular mechanisms, remodeling of the extracellular matrix, and the presence of growth factors. The problem of wound healing is associated with injuries in wars, population aging, and the increase in obesity and diabetes mellitus on a global scale. It is known that the wound healing process is significantly affected by obesity. In this regard, studies of the role of growth factors in wound healing in the development of obesity are relevant.

Purpose. To determine the dynamics of wound healing and growth factor concentrations in the skin during the healing of full-thickness excised linear wounds in rats of different sexes with glutamate-induced obesity.

Materials and methods. Newborn males and females (n = 64) were randomly divided into 4 groups. Group 1 (males) – control, in rats of this group at the age of 4 months, full-thickness excised linear wounds were simulated, which were not treated with anything. In 4-month-old rats of group 2 (males) with glutamate-induced obesity, full-thickness linear wounds were modeled. Group 3 (females) – control, in rats of this group at the age of 4 months, fullthickness linear wounds were modeled, which were not treated with anything. In 4-month-old rats of group 4 (females) with glutamate-induced obesity, fullthickness linear wounds were modeled. To induce obesity, rats of group 2 and group 4 were subcutaneously injected with a solution of monosodium glutamate at a dose of 4.0 mg/kg on the 2nd, 4th, 6th, 8th and 10th days after birth. The level of growth factors was determined using the appropriate reagent sets by the indirect enzyme-linked immunosorbent assay (ELISA) method according to the standard protocol.

Results. It has been shown that in male and female rats, the effect of glutamate-induced obesity on wound length is manifested only on the 12th day of healing. In males, the wound length in obesity during this period is 1.3 times higher (p < 0.05), and in females it is 1.4 times higher (p < 0.05) compared to the control. On the 16th day, males in the control have complete wound healing, and in obesity only on the 20th day. A similar picture is observed on the 16th day in females, in which complete healing also occurs on the 20th day. In male rats with glutamate-induced obesity, the concentration of insulin-like growth factor (IGF) significantly increases by 1.5 times compared to controls without obesity. In females, no difference in IGF concentration was found in the control and in obesity. However, in females, the concentration of IGF in obesity was 1.4 times higher than in obese males (p < 0.05). In obese females, the concentration of EGF was 1.4 times higher, FGF was 1.5 times higher, PDGF was 1.4 times higher, TGF was 1.3 times higher than in obese males/ However, no significant difference in the concentrations of NGF and VEGF was found in obesity between males and females.

Conclusions. In males and females with glutamate-induced obesity, wound healing occurs 4 days later than in controls without obesity. This process involves the growth factors IGF, EGF, FGF, PDGF and TGF, the concentration of which significantly increases in obesity. No significant difference in the concentrations of NGF and VEGF was found between males and females in both controls and obesity.

Ключові слова: glutamate-induced obesity, full-thickness linear incision wounds, male and female rats, growth factors

Повний текст: PDF (Ukr)

Список літератури
  1. Mamun AA, Shao C, Geng P, Wang S and Xiao J. Recent advances in molecular mechanisms of skin wound healing and its treatments. Front Immunol. 2024;15:1395479. doi.org/10.3389/fimmu.2024.1395479
  2. Díaz-García D, Filipová A, Garza-Veloz I, Martinez-Fierro ML. A beginner’s introduction to skin stem cells and wound healing. Int J Mol Sci. 2021;22:11030. doi.org/10.3390/ijms222011030
  3. Aragona M, Dekoninck S, Rulands S, Lenglez S, Mascré G, Simons BD, et al. Defining stem cell dynamics and migration during wound healing in mouse skin epidermis. Nat Commun. 2017;8:14684.doi.org/10.1038/ncomms14684
  4. Chou WC, Takeo M, Rabbani P, Hu H, Lee W, Chung YR, et al. Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat Med. 2013;19:924–929. doi.org/10.1038/nm.3194
  5. Leclère FM. The use of integra® Dermal regeneration template versus flaps for reconstruction of full-thickness scalp defects involving the calvaria: A cost-benefit analysis. Aesthetic Plast Surg. 2017;41:472–473. doi.org/10.1007/s00266-016-0765-z
  6. Boyce ST, Lalley AL. Tissue engineering of skin and regenerative medicine for wound care. Burn Trauma. 2018;6:4. doi.org/10.1186/s41038-017-0103-y
  7. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: A cellular perspective. Physiol Rev. 2019;99:665–706.doi.org/10.1152/physrev.00067.2017
  8. Tottoli EM, Dorati R, Genta I, Chiesa E, Pisani S, Conti B. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics. 2020;12:1–30.doi.org/10.3390/pharmaceutics12080735
  9. Nussbaum SR, Carter MJ, Fife CE, DaVanzo J, Haught R, Nusgart M, et al. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds. Value Heal. 2018;21:27–32.doi.org/10.1016/j.jval.2017.07.007
  10. Dreifke MB, Jayasuriya AA, Jayasuriya AC. Current wound healing procedures and potential care. Mater Sci Eng C. 2015;48:651–662. doi.org/10.1016/j.msec.2014.12.068
  11. Armstrong DG, Swerdlow MA, Armstrong AA, Conte MS, Padula WV, Bus SA. Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. J Foot Ankle Res. 2020;13:16. doi.org/10.1186/s13047-020-00383-2
  12. Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res. 2017;58:81–94. doi.org/10.1159/000454919
  13. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012; 18:673–683.doi.org/10.1038/nm.2731
  14. Sinno H, Prakash S. Complements and the wound healing cascade: an updated review.Plast Surg Int. 2013;2013:1–7. doi.org/10.1155/2013/146764
  15. Wang Z, Wang Y, Bradbury N, Bravo CG, Schnabi B, Di Nardo A. Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in kerationocytes. Sci Rep. 2020;10(1):21732. doi.org/10.1038/s41598-020-78244-y
  16. Matwiejuk M, Myśliwiec H, Chabowski A, Flisiak I. An Overview of Growth Factors as the Potential Link between Psoriasis and Metabolic Syndrome. J Clin Med. 2023;13(1):109.doi.org/10.3390/jcm13010109
  17. Wang X-R, Wang W-J, Yu X, Hua X, Ouyang F, Luo Z-C. Insulin-Like Growth Factor Axis Biomarkers and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis. Front. Endocrinol. 2019;10:444. doi.org/10.3389/fendo.2019.00444
  18. Sanabria ER, Pereira MF, Dolnikoff MS, et al. Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats. Brain Res Bull. 2002;59(1):47-51. doi.org/10.1016/s0361-9230(02)00837-7
  19. Bernardis LL, Patterson BD. Correlation between ’Lee index’ and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol. 1968;40:527–528.
  20. Crowther JR. The ELISA Guidebook. Totowa, New Jersey: Humana Press Inc., 2001, 436 p.
  21. Bartke A. Growth Hormone and Aging: Updated Review. World J Mens Health. 2019;37(1):19-30.doi.org/10.5534/wjmh.180018
  22. Laron Z. Insulin-like growth factor 1 (IGF-1): A growth hormone. Molecular Pathology. 2001;54(5):311-316. doi.org/10.1136/mp.54.5.311
  23. Tito C, Masciarelli S, Colotti G, Fazi F. EGF receptor in organ development, tissue homeostasis and regeneration. J Biomed Sci. 2025;32(1):24. Published 2025 Feb 19.doi.org/10.1186/s12929-025-01119-9
  24. Takehara K. Growth regulation of skin fibroblasts. J Dermatol Sci. 2000;24 Suppl 1:S70-S77. doi.org/10.1016/s0923-1811(00)00144-4
  25. Mokito T, Jinnin M, Muchemwa FC, et al. Basic fibroblast growth factor stimulates the proliferation of human dermal fibroblasts via the ERK1/2 and JNK pathways. British Journal of Dermatology. 2010;162(4):717–723. doi.org/10.1111/j.1365-2133.2009.09581.x
  26. Massagué J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 2000;1(3):169-178. doi.org/10.1038/35043051
  27. Kale A, Joshi S, Pillai A, Naphade N, Raju M, Nasrallah H, Mahadik SP. Reduced cerebrospinal fluid and plasma nerve growth factor in drug-naïve psychotic patients. Schizophrenia Research. 2009;115(2–3):209–214. doi.org/10.1016/j.schres.2009.07.022
  28. Amo Y, Masuzawa M, Hamada Y, Katsuoka K. Serum concentrations of vascular endothelial growth factor-D in angiosarcoma patients. British Journal of Dermatology. 2004;150(1):160–161.doi.org/10.1111/j.1365-2133.2004.05751.x
  29. Beato S, Ecker-Eckhofen G, Shao C, Piferrer F. Genetic, endocrine and epigenetic mechanisms underlying sexual size dimorphism in fish. Sex Dev. 2026;22:1–20. doi.org/10.1159/000550574
  30. Fernández-Pérez L, de Mirecki-Garrido M, Guerra B, Díaz M, Díaz-Chico JC. Sex steroids and growth hormone interactionsEsteroides sexuales e interacciones con la hormona de crecimiento. Endocrinología y Nutrición. 2016;63(4):171–180. doi.org/10.1016/j.endonu.2015.11.004
  31. Ogunmoroti O, Osibogun O, Zhao D, Mehta RC, Ouyang P, Lutsey PL, Robinson-Cohen C, Michos ED. Associations between endogenous sex hormones and FGF-23 among women and men in the Multi-Ethnic Study of Atherosclerosis. PLoS One. 2022;17(5):e0268759. doi.org/10.1371/journal.pone.0268759
  32. Bisgaard A, Sørensen K, Johannsen TH, Helge JW, Andersson AM, Juul A. Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adoles- cents. Int J Pediatr Endocrinol. 2014;2014(1):7.doi.org/10.1186/1687-9856-2014-7
  33. Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol.2016;78:223-241. doi.org/10.1146/annurev-physiol-021115-105339


Програмування - Roman.im | QR-Code Generator