urmjУральский медицинский журналUral Medical Journal2949-4389Ural State Medical University10.52420/2071-5943-2023-22-1-57-62urmj-1192Research ArticleОригинальные статьи | Original articlesOriginal articlesНарушение баланса ангиогенных и нейрогенных полипепитидов ротовой жидкости при переломах верхней челюстиImpairment of the balance of angiogenic and neurogenic polypeptides of the oral fluid in fractures of the maxillahttps://orcid.org/0000-0003-0966-9571БазарныйВ. В.BazarnyiV. V.

Владимир Викторович Базарный – доктор медицинских наук, профессор 

Екатеринбург

Vladimir V. Bazarnyi – Doctor of Science (Medicine), Professor 

Ekaterinburg

vlad-bazarny@yandex.ruhttps://orcid.org/0000-0002-8439-3272МандраЮ. В.MandraYu. V.

Юлия Владимировна Мандра – доктор медицинских наук, профессор 

Екатеринбург

 

Julija V. Mandra – Doctor of Science (Medicine), Professor 

Ekaterinburg

jmandra@mail.ruhttps://orcid.org/0000-0002-6092-3734КопенкинМ. А.KopenkinM. A.

Максим Александрович Копенкин 

Екатеринбург

Maksim A. Kopenkin 

Ekaterinburg

maximkopenkin@yandex.ruhttps://orcid.org/0000-0003-2295-0333АбдулкеримовТ. Х.AbdulkerimovT. Kh.

Тимур Хийирович Абдулкеримов 

Екатеринбург

Timur Kh. Abdulkerimov 

Ekaterinburg

tabdulkerimov05@gmail.comhttps://orcid.org/0000-0001-8412-4315МаксимоваА. Ю.MaximovaA. Yu.

Арина Юрьевна Максимова – кандидат медицинских наук 

Екатеринбург

Arina Yu. Maximova – Ph.D. in medicine 

Ekaterinburg

oreshek92@list.ruhttps://orcid.org/0000-0002-4921-7222ПолушинаЛ. Г.PolushinaL. G.

Лариса Георгиевна Полушина – кандидат медицинских наук 

Екатеринбург

Larisa G. Polushina – Ph.D. in medicine 

Ekaterinburg

polushina-larisa@bk.ruУральский государственный медицинский университетРоссияUral State Medical UniversityRussian Federation2023160320232215762Copyright © Базарный В.В., Мандра Ю.В., Копенкин М.А., Абдулкеримов Т.Х., Максимова А.Ю., Полушина Л.Г., 20232023Базарный В.В., Мандра Ю.В., Копенкин М.А., Абдулкеримов Т.Х., Максимова А.Ю., Полушина Л.Г.Bazarnyi V.V., Mandra Y.V., Kopenkin M.A., Abdulkerimov T.K., Maximova A.Y., Polushina L.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.umjusmu.ru/jour/article/view/1192

Введение. Переломы верхней челюсти в области орбиты характеризуются такими особенностями, как близкое расположение жизненно важных анатомических структур, органа зрения, а также эстетической значимостью данной зоны лица и наличием рисков развития серьезных осложнений . Цель работы – оценить уровень ангиогенных факторов в ротовой жидкости: фактора роста эндотелия сосудов А (VEGF-A), фактора роста эндотелия сосудов D (VEGF-D), плацентарного фактора роста (PIGF), тромбоцитарного фактора роста ВВ (PDGF-BB) (VEGF-A, VEGF-D, PIGF, PDGF-BB) и ней ротрофинов: фактора роста нервов (NGFb) и основного мозгового ней ротрофического фактора (BDNF) при переломах верхней челюсти в области орбиты. Материалы и методы. Проведено одноцентровое, открытое, проспективное исследование типа «случай – контроль», в котором обследовано 10 пациентов с переломом верхней челюсти в области нижней стенки орбиты (основная группа) и 10 практически здоровых добровольцев (группа сравнения). Наряду с клинико-инструментальным и лабораторным исследованием пациентам проводили определение содержания VEGF-A, VEGF-D, PIGF, PDGF-BB, NGFb и BDNF в ротовой жидкости методом мультипараметрического флуоресцентного анализа с магнитными микросферами (технология xMAP, Luminex 200, USA). Результаты. Содержание VEGF-A, VEGF-D, NGFb существенно не различалось у травмированных пациентов и практически здоровых добровольцев. Содержание PIGF-1 и PDGF-BB заметно повышалось при переломе верхней челюсти, причем концентрация последнего была в 12 раз выше, чем в группе сравнения. Обсуждение. Результаты свидетельствуют о том, что такие травмы сопровождаются нарушением баланса ангиогенных и ней рогенных полипептидов, проявляющегося повышением уровня плацентарного фактора роста, тромбоцитарного фактора роста и основного мозгового ней ротрофического фактора. Заключение. Изучение процессов ремоделирования сосудистой сети и ней ропротекции важно не только при обширных скелетных и черепно-мозговых травмах, но и при относительно локальной травме – переломе костей черепа в области орбиты.

Introduction. Fractures of the maxilla are characterized by such features as the close location of vital anatomical structures, the visual organ, as well as the aesthetic importance of this area of the face and the presence of risk of serious complications. The aim of the work was to estimate the level of angiogenic factors in the oral fluid: vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor D (VEGF-D), placental growth factor (PIGF), platelet-derived growth factor BB (PDGF-BB) (VEGF-A, VEGF-D, PIGF, PDGF-BB) and neurotrophins: nerve growth factor (NGFb) and basic brain-derived neurotrophic factor (BDNF) in orbital maxilla fractures. Materials and methods. A single-center, open-label, prospective case-control study was conducted in which 10 patients an upper jaw fracture of the maxilla (study group) and 10 practically healthy volunteers (comparison group) were examined. Along with clinical-instrumental and laboratory examination, patients were also examined for the content of VEGF-A, VEGF-D, PIGF, PDGF-BB, NGFb and BDNF in oral fluid by multiparametric fluorescent analysis with magnetic microspheres (xMAP technology, Luminex 200, USA). Results. The content of VEGF-A, VEGF-D, NGFb did not differ significantly between trauma patients and healthy practically volunteers. The content of PIGF-1 and PDGF-BB was markedly elevated in maxillary fracture, with the latter concentration being 12-fold higher than in the comparison group. Discussion. The results suggest that such injuries are accompanies by an imbalance of angiogenic and neurogenic polypeptides, manifested by increased levels of placental growth factor, platelet-derived growth factor and basic brain-derived neurotrophic factor. Conclusions. The study of the vascular remodeling and neuroprotection is important not only for extensive skeletal and craniocerebral trauma, but also for relatively local trauma – skull bone fracture in the orbit. 

перелом верхней челюстиангиогенные факторынейротрофиныfracture of the maxillaangiogenic factorsneurotrophinsРабота выполнена за счет средств государственного задания на научно-исследовательскую работу «Предикторы старения в полости рта и возможность их использования для персонификации стоматологического лечения». Регистрационный номер 121032300110-4 от 23.03.2021.The work was carried out at the expense of the state task for the research work "Predictors of aging in the oral cavity and the possibility of their use for the personalization of dental treatment". Registration number 121032300110-4 from 23.03.2021.ReferencesRamos JC, de Almeida MLD, de Alencar YCG et al. Epidemiological study of bucomaxilofacial trauma in a Paraíba reference hospital. Rev Col Bras Cir 2018;45(6):e1978. http://doi.org/10.1590/0100-6991e-20181978.Ramos JC, de Almeida MLD, de Alencar YCG et al. Epidemiological study of bucomaxilofacial trauma in a Paraíba reference hospital. Rev Col Bras Cir 2018;45(6):e1978. http://doi.org/10.1590/0100-6991e-20181978.Amin D, Al-Mulki K, Henriquez OA et al. Review of orbital fractures in an urban level I Trauma Center. Craniomaxillofac Trauma Reconstr 2020;13(3):174–179. http://doi.org/10.1177/1943387520924515.Amin D, Al-Mulki K, Henriquez OA et al. Review of orbital fractures in an urban level I Trauma Center. Craniomaxillofac Trauma Reconstr 2020;13(3):174–179. http://doi.org/10.1177/1943387520924515.Ghosh R, Gopalkrishnan K. Facial Fractures. J Craniofac Surg 2018;29(4):e334–e340. http://doi.org/10.1097/SCS.0000000000004269.Ghosh R, Gopalkrishnan K. Facial Fractures. J Craniofac Surg 2018;29(4):e334–e340. http://doi.org/10.1097/SCS.0000000000004269.Ahmad WMAW, Noor NFM, Shaari R et al. The most common relationship of a midface fracture in maxillofacial trauma study. J Craniofac Surg 2021;32(4):1500–1503. http://doi.org/10.1097/SCS.0000000000007435.Ahmad WMAW, Noor NFM, Shaari R et al. The most common relationship of a midface fracture in maxillofacial trauma study. J Craniofac Surg 2021;32(4):1500–1503. http://doi.org/10.1097/SCS.0000000000007435.Secanho MS, Neto BFM, Mazzoni LP et al. Facial fractures related to soccer. J Craniofac Surg 2021;32(4):1636–1638. http://doi.org/10.1097/SCS.0000000000007575.Secanho MS, Neto BFM, Mazzoni LP et al. Facial fractures related to soccer. J Craniofac Surg 2021;32(4):1636–1638. http://doi.org/10.1097/SCS.0000000000007575.Jones CM, Schmalbach CE. Zygomaticomaxillary fractures. Facial Plast Surg Clin North Am 2022;30(1):47–61. http://doi.org/10.1016/j.fsc.2021.08.004.Jones CM, Schmalbach CE. Zygomaticomaxillary fractures. Facial Plast Surg Clin North Am 2022;30(1):47–61. http://doi.org/10.1016/j.fsc.2021.08.004.Wang HD, Dillon J. Contemporary management of zygomaticomaxillary complex fractures. Semin Plast Surg 2021;35(4):256–262. http://doi.org/10.1055/s-0041-1735812.Wang HD, Dillon J. Contemporary management of zygomaticomaxillary complex fractures. Semin Plast Surg 2021;35(4):256–262. http://doi.org/10.1055/s-0041-1735812.Матчин А.А., Носов Е.В., Кириакиди С.Х. Морфофункциональная оценка реорганизации нонапептидергических гипоталамических нейросекреторных центров при экспериментальных переломах нижней челюсти. Морфология 2020;157(2–3):137.Matchin AA, Nosov EV, Kiriakidi SH. Morpho-functional assessment of the reorganization of nonapeptidergic hypothalamic neurosecretory centers in experimental fractures of the lower jaw. Morphology 2020;157(2–3):137. (In Russ.).Паскова Е.В., Маркелова Е.В., Голицына А.А. с соавт. Патогенетическое обоснование применения рекомбинантных интерлейкинов у пациентов c переломами челюсти с целью профилактики посттравматического остеомиелита. Российский иммунологический журнал 2021;24(1):133–140. http://doi.org/10.46235/1028-7221-979-PRF.Paskova EV, Markelova EV, Golicyna AA et al. Pathogenetic rationale for usage of recombinant interleukins in the patients with mandibular fractures to prevent post-traumatic osteomyelitis. Russian Journal of Immunology 2021;24(1):133–140. (In Russ.) http://doi.org/10.46235/1028-7221-979-PRF.Базарный В.В., Полушина Л.Г., Максимова А.Ю. с соавт. Патогенетическое обоснование новых подходов к оценке состояния тканей полости рта при хроническом генерализованном пародонтите. Терапевтическая стоматология 2018;14(4):14–18. http://doi.org/10.18481/2077-7566-2018-14-4-14-18.Bazarnyy VV, Polushina LG, Maksimova AY et al. Pathogenetic justification of new approaches to the assessment of the state of oral cavity in chronic generalized parodontitis. Actual problems in dentistry 2018;14(4):14–18. (In Russ.). https://doi.org/10.18481/2077-7566-2018-14-4-14-18.Engvall E, Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzymelabeled anti-immunoglobulin in antigen-coated tubes. J Immunol 1972;109(1):129–135.Engvall E, Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzymelabeled anti-immunoglobulin in antigen-coated tubes. J Immunol 1972;109(1):129–135.Filipowska J, Tomaszewski KA, Niedźwiedzki Ł et al. The role of vasculature in bone development, regeneration and proper systemic functioning. Angiogenesis 2017;20(3):291–302. http://doi.org/10.1007/s10456-017-9541-1.Filipowska J, Tomaszewski KA, Niedźwiedzki Ł et al. The role of vasculature in bone development, regeneration and proper systemic functioning. Angiogenesis 2017;20(3):291–302. http://doi.org/10.1007/s10456-017-9541-1.Barabaschi GD, Manoharan V, Li Q, Bertassoni LE. Engineering pre-vascularized scaffolds for bone regeneration. Adv Exp Med Biol 2015;881:79–94. http://doi.org/10.1007/978-3-319-22345-2_5.Barabaschi GD, Manoharan V, Li Q, Bertassoni LE. Engineering pre-vascularized scaffolds for bone regeneration. Adv Exp Med Biol 2015;881:79–94. http://doi.org/10.1007/978-3-319-22345-2_5.Lee EJ, Jain M, Alimperti S. Bone microvasculature: stimulus for tissue function and regeneration. Tissue Eng Part B Rev 2021;27(4):313–329. http://doi.org/10.1089/ten.TEB.2020.0154.Lee EJ, Jain M, Alimperti S. Bone microvasculature: stimulus for tissue function and regeneration. Tissue Eng Part B Rev 2021;27(4):313–329. http://doi.org/10.1089/ten.TEB.2020.0154.Diomede F, Marconi GD, Fonticoli L et al. Functional relationship between osteogenesis and angiogenesis in tissue regeneration. Int J Mol Sci 2020;21(9):3242. http://doi.org/10.3390/ijms21093242.Diomede F, Marconi GD, Fonticoli L et al. Functional relationship between osteogenesis and angiogenesis in tissue regeneration. Int J Mol Sci 2020;21(9):3242. http://doi.org/10.3390/ijms21093242.Pulcini S, Merolle L, Marraccini C et al. Apheresis platelet rich-plasma for regenerative medicine: an in vitro study on osteogenic potential. Int J Mol Sci 2021;22(16):8764. http://doi.org/10.3390/ijms22168764.Pulcini S, Merolle L, Marraccini C et al. Apheresis platelet rich-plasma for regenerative medicine: an in vitro study on osteogenic potential. Int J Mol Sci 2021;22(16):8764. http://doi.org/10.3390/ijms22168764.Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol 2012;8(7):390–398. http://doi.org/10.1038/nrrheum.2012.80.Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol 2012;8(7):390–398. http://doi.org/10.1038/nrrheum.2012.80.Lazarovici P, Lahiani A, Gincberg G et al. Nerve growth factor-induced angiogenesis: 1. Endothelial cell tube formation assay. Methods Mol Biol 2018;1727:239–250. http://doi.org/10.1007/978-1-4939-7571-6_18.Lazarovici P, Lahiani A, Gincberg G et al. Nerve growth factor-induced angiogenesis: 1. Endothelial cell tube formation assay. Methods Mol Biol 2018;1727:239–250. http://doi.org/10.1007/978-1-4939-7571-6_18.Peng Y, Wu S, Li Y, Crane JL. Type H blood vessels in bone modeling and remodeling. Theranostics 2020;10(1):426–436. http://doi.org/10.7150/thno.34126.Peng Y, Wu S, Li Y, Crane JL. Type H blood vessels in bone modeling and remodeling. Theranostics 2020;10(1):426–436. http://doi.org/10.7150/thno.34126.Shen Z, Chen Z, Li Z et al. Total Flavonoids of rhizoma drynariae enhances angiogenic-osteogenic coupling during distraction osteogenesis by promoting type H vessel formation through PDGF-BB/PDGFR-β instead of HIF-1α/ VEGF axis. Front Pharmacol 2020;11:503524. http://doi.org/10.3389/fphar.2020.503524.Shen Z, Chen Z, Li Z et al. Total Flavonoids of rhizoma drynariae enhances angiogenic-osteogenic coupling during distraction osteogenesis by promoting type H vessel formation through PDGF-BB/PDGFR-β instead of HIF-1α/ VEGF axis. Front Pharmacol 2020;11:503524. http://doi.org/10.3389/fphar.2020.503524.Zhang J, Pan J, Jing W. Motivating role of type H vessels in bone regeneration. Cell Prolif 2020;53(9):e12874. http://doi.org/10.1111/cpr.12874.Zhang J, Pan J, Jing W. Motivating role of type H vessels in bone regeneration. Cell Prolif 2020;53(9):e12874. http://doi.org/10.1111/cpr.12874.Gianni-Barrera R, Butschkau A, Uccelli A et al. PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation. Angiogenesis 2018;21(4):883–900. http://doi.org/10.1007/s10456-018-9634-5.Gianni-Barrera R, Butschkau A, Uccelli A et al. PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation. Angiogenesis 2018;21(4):883–900. http://doi.org/10.1007/s10456-018-9634-5.Banfi A, von Degenfeld G, Gianni-Barrera R et al. Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. FASEB J 2012;26(6):2486–2497. http://doi.org/10.1096/fj.11-197400.Banfi A, von Degenfeld G, Gianni-Barrera R et al. Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. FASEB J 2012;26(6):2486–2497. http://doi.org/10.1096/fj.11-197400.Macarulla T, Montagut C, Sánchez-Martin FJ et al. The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls. Expert Opin Biol Ther 2020;20(1):15-22. http://doi.org/10.1080/14712598.2020.Macarulla T, Montagut C, Sánchez-Martin FJ et al. The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls. Expert Opin Biol Ther 2020;20(1):15-22. http://doi.org/10.1080/14712598.2020.Kankanamalage OM, Zhou Q, Li X. Understanding the pathogenesis of gestational hypothyroidism. Front Endocrinol (Lausanne) 2021:12:653407. http://doi.org/10.3389/fendo.2021.653407.Kankanamalage OM, Zhou Q, Li X. Understanding the pathogenesis of gestational hypothyroidism. Front Endocrinol (Lausanne) 2021:12:653407. http://doi.org/10.3389/fendo.2021.653407.De Falco S. The discovery of placenta growth factor and its biological activity. Exp Mol Med 2012;44(1):1–9. http://doi.org/10.3858/emm.2012.44.1.025.De Falco S. The discovery of placenta growth factor and its biological activity. Exp Mol Med 2012;44(1):1–9. http://doi.org/10.3858/emm.2012.44.1.025.Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2011;2(12):1097–1105. http://doi.org/10.1177/1947601911423031.Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2011;2(12):1097–1105. http://doi.org/10.1177/1947601911423031.Mariotti V, Fiorotto R, Cadamuro M et al. New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Rep 2021;3(3):100251. http://doi.org/10.1016/j.jhepr.2021.100251.Mariotti V, Fiorotto R, Cadamuro M et al. New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Rep 2021;3(3):100251. http://doi.org/10.1016/j.jhepr.2021.100251.Базарный В.В., Копенкин М.А. Клиническая ценность определения белка в перикардиальной жидкости. Лабораторная служба 2022;11(1):58–60. http://doi.org/10.17116/labs20221101158.Bazarnyj VV, Kopenkin MA. Clinical value of protein determination in pericardial fluid. Laboratory Service = Laboratornaja sluzhba 2022;11(1):58–60 (In Russ.) http://doi.org/10.17116/labs20221101158.Базарный В.В., Полушина Л.Г., Ваневская Е.А. Иммунологический анализ ротовой жидкости как потенциальный диагностический инструмент. Российский иммунологический журнал 2014;8(3–17):769–771.Bazarnyj VV, Polushina LG, Vanevskaja EA. Immunoassay of oral fluid as a potential diagnostic tool. Russian Journal of Immunology 2014;8(3–17):769–771. (In Russ.).Gustafsson D, Klang A, Thams S, Rostami E. The role of BDNF in experimental and clinical traumatic brain injury. Int J Mol Sci 2021;22(7):3582. http://doi.org/10.3390/ijms22073582.Gustafsson D, Klang A, Thams S, Rostami E. The role of BDNF in experimental and clinical traumatic brain injury. Int J Mol Sci 2021;22(7):3582. http://doi.org/10.3390/ijms22073582.Rostami E, Krueger F, Plantman S et al. Alteration in BDNF and its receptors, full-length and truncated TrkB and p75(NTR) following penetrating traumatic brain injury. Brain Res 2014;1542:195–205. http://doi.org/10.1016/j.brainres.2013.10.047.Rostami E, Krueger F, Plantman S et al. Alteration in BDNF and its receptors, full-length and truncated TrkB and p75(NTR) following penetrating traumatic brain injury. Brain Res 2014;1542:195–205. http://doi.org/10.1016/j.brainres.2013.10.047.Wu YC, Ning L, Tu YK et al. Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population. J Formos Med Assoc 2018;117(9):841–848. http://doi.org/10.1016/j.jfma.2017.10.004.Wu YC, Ning L, Tu YK et al. Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population. J Formos Med Assoc 2018;117(9):841–848. http://doi.org/10.1016/j.jfma.2017.10.004.Şaştım ÇY, Gürsoy M, Könönen E et al. Salivary and serum markers of angiogenesis in periodontitis in relation to smoking. Clin Oral Investig 2021;25(3):1117–1126. http://doi.org/10.1007/s00784-020-03411-4.Şaştım ÇY, Gürsoy M, Könönen E et al. Salivary and serum markers of angiogenesis in periodontitis in relation to smoking. Clin Oral Investig 2021;25(3):1117–1126. http://doi.org/10.1007/s00784-020-03411-4.Upile T, Jerjes W, Kafas P et al. Salivary VEGF: a non-invasive angiogenic and lymphangiogenic proxy in head and neck cancer prognostication. Int Arch Med 2009;2(1):12. http://doi.org/10.1186/1755-7682-2-12.Upile T, Jerjes W, Kafas P et al. Salivary VEGF: a non-invasive angiogenic and lymphangiogenic proxy in head and neck cancer prognostication. Int Arch Med 2009;2(1):12. http://doi.org/10.1186/1755-7682-2-12.Polz-Dacewicz M, Strycharz-Dudziak M, Dworzański J et al. Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections. Infect Agent Cancer 2016;11:45. http://doi.org/10.1186/s13027-016-0093-6.Polz-Dacewicz M, Strycharz-Dudziak M, Dworzański J et al. Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections. Infect Agent Cancer 2016;11:45. http://doi.org/10.1186/s13027-016-0093-6.

The authors declare that there are no conflicts of interest present.