2658-6533Научные результаты биомедицинских исследований2658-653310.18413/2658-6533-2026-12-2-0-84158Клиническая медицина<strong>Взаимосвязь между фактором роста фибробластов 21 (FGF-21) и клинико-лабораторными показателями у пациенток гериатрического профиля с ревматоидным артритом</strong><strong>The relationship between fibroblast growth factor 21 (FGF-21) and clinical and laboratory parameters in geriatric patients with rheumatoid arthritis</strong><br /> &nbsp;АхвердянЮрий РубеновичAkhverdyanYury R.doctor_2001@mail.ruПапичевЕвгений ВасильевичPapichevEugene V.e_papichev@mail.ruЗаводовскийБорис ВалерьевичZavodovskyBoris V.pebma@pebma.ruПоляковаЮлия ВасильевнаPolyakovaYulia V.jpolyakova@yandex.ruСивордоваЛариса ЕвгеньевнаSeewordovaLarissa E.seeword@mail.ru202612200

Актуальность: Известно, что системный уровень FGF-21 связан с ожирением и воспалительными цитокинами, а также со снижением функционального состояния при ревматоидном артрите (РА). Возможно моделирование тяжести течения РА у мышей путем введения экзогенного FGF-21. Все эти факты свидетельствуют о важной роли FGF-21 в прогрессировании данного заболевания. Известно, что концентрация FGF-21 в сыворотке крови положительно коррелирует с возрастом. Учитывая связь между FGF-21, метаболическими изменениями и наличием хронического воспаления, можно предположить наличие определенных корреляций у пожилых пациентов с РА. Цель исследования: Изучить взаимосвязи между уровнем FGF-21 сыворотки крови и клинико-лабораторными показателями у пожилых пациенток с ревматоидным артритом. Материалы и методы: Под нашим наблюдением находилось 88 женщин с верифицированным диагнозом РА, средний возраст пациенток составил 67,3&plusmn;4,8 (60,7-74,5) лет. Активность болезни по DAS 28 составила 3,52&plusmn;1,14 (3,28-3,76) баллов. Базисная терапия больных РА соответствовала клиническим рекомендациям. Результаты: Была выявлена положительная корреляция между системным уровнем FGF-21 и весом, а также ИМТ (p&lt;0,0001), отрицательная корреляция с длительностью течения РА (&rho;=-0,22; p=0,041). Также обнаружена взаимосвязь между уровнем FGF-21 и наличием сахарного диабета 2-го типа (p=0,027). Других корреляций с коморбидными состояниями, в том числе с наличием остеопороза и остеопоретических переломов, выявлено не было. Выявлено, что уровень FGF-21 в сыворотке крови был достоверно выше у пациенток, принимающих глюкокортикостероиды на момент исследования (p=0,001). Заключение: Дальнейшее изучение значения FGF-21 у пациентов с РА открывает широкие перспективы для использования данного миокина в качестве лекарственного средства или терапевтической мишени

Background: Systemic FGF-21 levels are known to be associated with obesity and inflammatory cytokines, and with reduced functional status in rheumatoid arthritis (RA). It is possible to model the severity of RA in mice by administering exogenous FGF-21. All these facts indicate an important role of FGF-21 in the progression of this disease. It is known that the concentration of FGF-21 in blood serum is positively correlated with age. Given the association between FGF-21, metabolic changes, and the presence of chronic inflammation, certain correlations can be hypothesized in older RA patients. The aim of the study: To study the relationship between serum FGF-21 levels and clinical and laboratory parameters in elderly patients with rheumatoid arthritis. Materials and methods: We observed 88 women with a verified diagnosis of RA; the average age of the patients was 67.4&plusmn;6.9 (61.7-73.4) years. Disease activity according to DAS 28 was 3.52&plusmn;1.14 (3.28-3.76) points. Basic therapy for patients with RA complied with clinical recommendations. Results: A positive correlation was found between the systemic level of FGF-21 and weight, as well as BMI (p&lt;0.0001), and a negative correlation with the duration of RA (&rho;=-0.22; p=0.041). A relationship was also found between the level of FGF-21 and the presence of type 2 diabetes mellitus (p=0.027). There were no other correlations with comorbid conditions, including the presence of osteoporosis and osteoporetic fractures. It was found that the level of FGF-21 in the blood serum was significantly higher in patients taking glucocorticosteroids at the time of the study (p=0.001). Conclusion: Further study of the significance of FGF-21 in patients with RA opens up broad prospects for the use of this myokine as a drug or therapeutic target

фактор роста фибробластовFGF-21инсулинорезистентностьметаболический синдромревматоидный артритfibroblast growth factorFGF-21insulin resistancemetabolic syndromerheumatoid arthritisСписок литературыWhitham M, Febbraio M. A. The ever-expanding myokinome: discovery challenges and therapeutic implications. Nature Reviews Drug Discovery. 2016;15:719-729. DOI: https://doi.org/10.1038/nrd.2016.153Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nature Reviews Endocrinology. 2020;16(11):654-667. DOI: https://doi.org/10.1038/s41574-020-0386-0Lewis JE, Ebling FJP, Samms RJ, et al. Going back to the biology of FGF-21: New insights.&nbsp;Trends in Endocrinology and Metabolism. 2019;30(8):491-504. DOI: https://doi.org/10.1016/j.tem.2019.05.007Kliewer SA, Mangelsdorf DJ. A dozen years of discovery: Insights into the physiology and pharmacology of FGF-21. Cell Metabolism. 2019;29(2):246-253. DOI: https://doi.org/10.1016/j.cmet.2019.01.004Lewis JE, Monnier C, Marshall H, et al. Whole-body and adipose tissue-specific mechanisms underlying the metabolic effects of fibroblast growth factor 21 in the Siberian hamster. Molecular Metabolism. 2020;31:45-54. DOI: https://doi.org/10.1016/j.molmet.2019.10.009Praktiknjo M, Djayadi N, Mohr R, et al.&nbsp;Fibroblast growth factor 21 is independently associated with severe hepatic steatosis in non-obese HIV-infected patients. Liver International. 2019;39(8):1514-1520. DOI: https://doi.org/10.1111/liv.14107Shi Y, Lu W, Hou Y, et al. Fibroblast growth factor 21 ameliorates vascular calcification by inhibiting osteogenic transition in vitamin D3 plus nicotine-treated rats. Biochemical and Biophysical Research Communications. 2018;495(4):2448-2455. DOI: https://doi.org/10.1016/j.bbrc.2017.10.115Tan H, Yue T, Chen Z, et al. Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine. International Journal of Biological Sciences. 2023;19(1):66-88. DOI: https://doi.org/10.7150/ijbs.73936Samms RJ, Lewis JE, Norton L, et al. FGF-21 is an insulin-dependent postprandial hormone in adult humans. Journal of Clinical Endocrinology and Metabolism. 2017;102(10):3806-3813. DOI: https://doi.org/10.1210/jc.2017-01257Wu L, Qian L, Zhang L, et al. Fibroblast growth factor 21 is related to atherosclerosis independent of nonalcoholic fatty liver disease and predicts atherosclerotic cardiovascular events. Journal of the American Heart Association. 2020;9(11):e015226. DOI: https://doi.org/10.1161/JAHA.119.015226Ong KL, Hui N, Januszewski AS, et al. High plasma FGF21 levels predicts major cardiovascular events in patients treated with atorvastatin (from the Treating to New Targets [TNT] Study). Metabolism. 2019;93:93-99. DOI: https://doi.org/10.1016/j.metabol.2018.11.006Kohara M, Masuda T, Shiizaki K, et al. Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease. PLoS ONE. 2017;12:e0178971. DOI: https://doi.org/10.1371/journal.pone.0178971Lee CH, Woo YC, Chow WS, et al. Role of circulating fibroblast growth factor 21 measurement in primary prevention of coronary heart disease among chinese patients with type 2 diabetes mellitus. Journal of the American Heart Association. 2017;6(6):e005344. DOI: https://doi.org/10.1161/JAHA.116.005344Conte M, Ostan R, Fabbri C, et al. Human aging and longevity are characterized by high levels of mitokines. Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2019;74(5):600-607. DOI: https://doi.org/10.1093/gerona/gly153Bian J, Chen L, Li Q, et al. Relationship between Serum FGF-21 and vWF Expression and Carotid Atherosclerosis in Elderly Patients with Hypertension. Journal of Healthcare Engineering. 2022;2022:6777771. DOI: https://doi.org/10.1155/2022/6777771Phrommintikul A, Sa-Nguanmoo P, Sripetchwandee J, et al. Factors associated with cognitive impairment in elderly versus nonelderly patients with metabolic syndrome: the different roles of FGF-21. Scientific Reports. 2018;8(1):5174. DOI: https://doi.org/10.1038/s41598-018-23550-9Franz K, Ost M, Otten L, et al. Higher serum levels of fibroblast growth factor 21 in old patients with cachexia. Nutrition. 2019;63-64:81-86. DOI: https://doi.org/10.1016/j.nut.2018.11.004Zhao M, Jung Y, Jiang Z, et al. Regulation of energy metabolism by receptor tyrosine kinase ligands. Frontiers in Physiology. 2020;11:354. DOI: https://doi.org/10.3389/fphys.2020.00354Staiger H, Keuper M, Berti L, et al. Fibroblast growth factor 21-metabolic role in mice and men.&nbsp;Endocrine Reviews. 2017;38(5):468-488. DOI: https://doi.org/10.1210/er.2017-00016Gould PW, Zemel BS, Taratuta EG, et al. Circulating Fibroblast Growth Factor-21 Levels in Rheumatoid Arthritis: Associations With Disease Characteristics, Body Composition, and Physical Functioning. Journal of Rheumatology. 2021;48(4):504-512. DOI: https://doi.org/10.3899/jrheum.200673Baker JF, Katz P, Weber DR, et al. Adipocytokines and Associations With Abnormal Body Composition in Rheumatoid Arthritis. Arthritis Care and Research. 2023;75(3):616-624. DOI: https://doi.org/10.1002/acr.24790Opoku YK, Liu Z, Liu H, et al. Fibroblast Growth Factor&ndash;21 Ameliorates Rheumatoid Arthritis by Maintaining Articular Integrity. International Journal of Peptide Research and Therapeutics. 2020;26:651-659. DOI: https://doi.org/10.1007/s10989-019-09872-wFederico LE, Johnson TM, England BR, et al. Circulating Adipokines and Associations With Incident Cardiovascular Disease in Rheumatoid Arthritis. Arthritis Care and Research. 2023;75(4):768-777. DOI: https://doi.org/10.1002/acr.24885Ebrahimi F, Urwyler SA, Betz MJ, et al. Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome. Scientific Reports. 2021;11(1):7911. DOI: https://doi.org/10.1038/s41598-021-87207-wPatel R, Bookout AL, Magomedova L, et al. Glucocorticoids regulate the metabolic hormone FGF-21 in a feed-forward loop. Molecular Endocrinology. 2015;29(2):213-223. DOI: https://doi.org/10.1210/me.2014-1259Guan Y, Huang J, Huanget S, et al. FGF-21 mediates corticosteroid-related bone mass loss through PPAR-&gamma;. In: 2019 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). San Diego, CA, USA: IEEE; 2019. DOI: https://doi.org/10.1109/BIBM47256.2019.8983042Larson KR, Jayakrishnan D, Soto Sauza KA, et al. FGF-21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids. Endocrinology. 2024;165(3):bqae004. DOI: https://doi.org/10.1210/endocr/bqae004Sun X, Xie YZ, Jiang YY, et al. FGF21 Enhances Therapeutic Efficacy and Reduces Side Effects of Dexamethasone in Treatment of Rheumatoid Arthritis. Inflammation. 2021;44(1):249-260. DOI: https://doi.org/10.1007/s10753-020-01327-5&nbsp;