Циркадные ритмы печени и их половой диморфизм: современное состояние проблемы
https://doi.org/10.35401/2541-9897-2024-9-2-108-114
Аннотация
Ритмичность процессов функционирования жизнедеятельности на клеточном, органном и системном уровнях является одним из фундаментальных свойств живого. Среди широкого спектра биоритмов наиболее важными для млекопитающих являются циркадианные (циркадные) ритмы. У млекопитающих циркадные ритмы согласовывают протекание широкого спектра физиологических процессов c постоянно меняющимися условиями окружающей среды, в первую очередь, со световым режимом. Данные об особенностях циркадных ритмов печени – важнейшего органа поддержания гомеостаза – ограничены, а иногда и вовсе противоречивы. Целью настоящей статьи является анализ современных научных работ, посвященных вопросам организации суточных ритмов на генном, клеточном и органном уровнях. Актуальность данного обзора обусловлена тем, что за последние десятилетия накоплен значительный объем знаний о том, что нарушение нормальной циркадной ритмичности печени лежит в основе развития ряда тяжелых патологий. В статье освещены некоторые аспекты нормальной циркадной ритмичности функционирования печени и роли нарушения циркадных ритмов в возникновении некоторых патологий. Особое внимание уделено малоизученному вопросу половых различий в суточной ритмичности функционирования печени млекопитающих.
Об авторах
Д. А. Арешидзе
Научно-исследовательский институт морфологии человека им. акад. А.П. Авцына Российского научного центра хирургии им. акад. Б.В. Петровского
Россия
Россия
Арешидзе Давид Александрович, к. б. н., заведующий лаборатории патологии клетки
117418, Москва, ул. Цюрупы, д. 3
Л. В. Кактурский
Научно-исследовательский институт морфологии человека им. акад. А.П. Авцына Российского научного центра хирургии им. акад. Б.В. Петровского
Россия
Россия
Кактурский Лев Владимирович, д. м. н., профессор, член-корреспондент РАН, научный руководитель
Москва
Список литературы
1. Под ред. С.М. Чибисова, С.И. Рапопорта, М.Л. Благонравова. Хронобиология и хрономедицина. РУДН; 2018.
2. Walker WH 2nd, Bumgarner JR, Walton JC, et al. Light pollution and cancer. Int J Mol Sci. 2020;21(24):9360. PMID: 33302582. PMCID: PMC7764771. https://doi.org/10.3390/ijms21249360
3. Агаджанян Н.А., Макарова И.И. Магнитное поле Земли и организм человека. Экология человека. 2005;(9):3–9.
4. Татевосян А.С., Быков И.М., Губарева Д.А. Метаболическое влияние на циркадные осцилляции pH и Eh в моче и слюне. Инновационная медицина Кубани. 2022;7(4):82–89. https://doi.org/10.35401/2541-9897-2022-25-4-82-89
5. Zimmet P, Alberti KGMM, Stern N, et al. The circadian syndrome: is the metabolic syndrome and much more!. J Intern Med. 2019;286(2):181–191. PMID: 31081577. PMCID: PMC6851668. https://doi.org/10.1111/joim.12924
6. Michel S, Meijer JH. From clock to functional pacemaker. Eur J Neurosci. 2020;51(1):482–493. PMID: 30793396. PMCID: PMC7027845. https://doi.org/10.1111/ejn.14388
7. Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418(6901):935–941. PMID: 12198538. https://doi.org/10.1038/nature00965
8. Leng Y, Musiek ES, Hu K, et al. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019;18(3):307–318. PMID: 30784558. PMCID: PMC6426656. https://doi.org/10.1016/S1474-4422(18)30461-7
9. Kuljis DA, Loh DH, Truong D, et al. Gonadal- and sex-chromosome-dependent sex differences in the circadian system. Endocrinology. 2013;154(4):1501–1512. PMID: 23439698. PMCID: PMC3602630. https://doi.org/10.1210/en.2012-1921
10. Berthier A, Johanns M, Zummo FP, Lefebvre P, Staels B. PPARs in liver physiology. Biochim Biophys Acta Mol Basis Dis. 2021;1867(5):166097. PMID: 33524529. https://doi.org/10.1016/j.bbadis.2021.166097
11. Kim P, Oster H, Lehnert H, et al. Coupling the circadian clock to homeostasis: the role of period in timing physiology. Endocr Rev. 2019;40(1):66–95. PMID: 30169559. https://doi.org/10.1210/er.2018-00049
12. Takahashi JS, Hong HK, Ko CH, McDearmon EL. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet. 2008;9(10):764–775. PMID: 18802415. PMCID: PMC3758473. https://doi.org/10.1038/nrg2430
13. Koronowski KB, Kinouchi K, Welz PS, et al. Defining the independence of the liver circadian clock. Cell. 2019;177(6):1448–1462.e14. PMID: 31150621. PMCID: PMC6813833. https://doi.org/10.1016/j.cell.2019.04.025
14. Li H, Zhang S, Zhang W, et al. Endogenous circadian time genes expressions in the liver of mice under constant darkness. BMC Genomics. 2020;21(1):224. PMID: 32160860. PMCID: PMC7066782. https://doi.org/10.1186/s12864-020-6639-4
15. Flessa CM, Kyrou I, Nasiri-Ansari N, Kaltsas G, Kassi E, Randeva HS. Endoplasmic reticulum stress in nonalcoholic (metabolic associated) fatty liver disease (NAFLD/MAFLD). J Cell Biochem. 2022;123(10):1585–1606. PMID: 35490371. https://doi.org/10.1002/jcb.30247
16. Reinke H, Asher G. Circadian clock control of liver metabolic functions. Gastroenterology. 2016;150(3):574–580. PMID: 26657326. https://doi.org/10.1053/j.gastro.2015.11.043
17. Robles MS, Cox J, Mann M. In-vivo quantitative proteomics reveals a key contribution of post-transcriptional mechanisms to the circadian regulation of liver metabolism. PLoS Genet. 2014;10(1):e1004047. PMID: 24391516. PMCID: PMC3879213. https://doi.org/10.1371/journal.pgen.1004047
18. Sun R, Huang J, Yang N, et al. Purine catabolism shows a dampened circadian rhythmicity in a high-fat diet-induced mouse model of obesity. Molecules. 2019;24(24):4524. PMID: 31835615. PMCID: PMC6943701. https://doi.org/10.3390/molecules24244524
19. Akhtar RA, Reddy AB, Maywood ES, et al. Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Curr Biol. 2002;12(7):540–550. PMID: 11937022. https://doi.org/10.1016/s0960-9822(02)00759-5
20. Vollmers C, Gill S, DiTacchio L, Pulivarthy SR, Le HD, Panda S. Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A. 2009;106(50):21453–21458. PMID: 19940241. PMCID: PMC2795502. https://doi.org/10.1073/pnas.0909591106
21. Wang J, Mauvoisin D, Martin E, et al. Nuclear proteomics uncovers diurnal regulatory landscapes in mouse liver. Cell Metab. 2017;25(1):102–117. PMID: 27818260. PMCID: PMC5241201. https://doi.org/10.1016/j.cmet.2016.10.003
22. Zhang Y, Xi X, Mei Y, et al. High-glucose induces retinal pigment epithelium mitochondrial pathways of apoptosis and inhibits mitophagy by regulating ROS/PINK1/Parkin signal pathway. Biomed Pharmacother. 2019;111:1315–1325. PMID: 30841445. https://doi.org/10.1016/j.biopha.2019.01.034
23. McCommis KS, Butler AA. The importance of keeping time in the liver. Endocrinology. 2021;162(2):bqaa230. PMID: 33320193. PMCID: PMC7799431. https://doi.org/10.1210/endocr/bqaa230
24. Lamia KA, Storch KF, Weitz CJ. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A. 2008;105(39):15172–15177. PMID: 18779586. PMCID: PMC2532700. https://doi.org/10.1073/pnas.0806717105
25. Rudic RD, McNamara P, Curtis AM, et al. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2004;2(11):e377. PMID: 15523558. PMCID: PMC524471. https://doi.org/10.1371/journal.pbio.0020377
26. Zhang EE, Kay SA. Clocks not winding down: unravelling circadian networks. Nat Rev Mol Cell Biol. 2010;11(11):764–776. PMID: 20966970. https://doi.org/10.1038/nrm2995
27. Lamia KA, Papp SJ, Yu RT, et al. Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature. 2011;480(7378):552–556. PMID: 22170608. PMCID: PMC3245818. https://doi.org/10.1038/nature10700
28. Jeyaraj D, Scheer FA, Ripperger JA, et al. Klf15 orchestrates circadian nitrogen homeostasis. Cell Metab. 2012;15(3):311–323. PMID: 22405069. PMCID: PMC3299986. https://doi.org/10.1016/j.cmet.2012.01.020
29. Chaix A, Lin T, Le HD, Chang MW, Panda S. Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock. Cell Metab. 2019;29(2):303–319.e4. PMID: 30174302. PMCID: PMC7751278. https://doi.org/10.1016/j.cmet.2018.08.004
30. Adamovich Y, Aviram R, Asher G. The emerging roles of lipids in circadian control. Biochim Biophys Acta. 2015;1851(8):1017–1025. PMID: 25483623. https://doi.org/10.1016/j.bbalip.2014.11.013
31. Eckel-Mahan K, Sassone-Corsi P. Metabolism and the circadian clock converge. Physiol Rev. 2013;93(1):107–135. PMID: 23303907. PMCID: PMC3781773. https://doi.org/10.1152/physrev.00016.2012
32. Grimaldi B, Bellet MM, Katada S, et al. PER2 controls lipid metabolism by direct regulation of PPARγ. Cell Metab. 2010;12(5):509–520. PMID: 21035761. PMCID: PMC4103168. https://doi.org/10.1016/j.cmet.2010.10.005
33. Le Martelot G, Canella D, Symul L, et al; CycliX Consortium. Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles. PLoS Biol. 2012;10(11):e1001442. PMID: 23209382. PMCID: PMC3507959. https://doi.org/10.1371/journal.pbio.1001442
34. Frazier K, Chang EB. Intersection of the gut microbiome and circadian rhythms in metabolism. Trends Endocrinol Metab. 2020;31(1):25–36. PMID: 31677970. PMCID: PMC7308175. https://doi.org/10.1016/j.tem.2019.08.013
35. Bottalico LN, Weljie AM. Cross-species physiological interactions of endocrine disrupting chemicals with the circadian clock. Gen Comp Endocrinol. 2021;301:113650. PMID: 33166531. PMCID: PMC7993548. https://doi.org/10.1016/j.ygcen.2020.113650
36. Kalko KO. Chronopharmacological Study of the Activity of Hepatoprotective Medicines. Dissertation abstract. National University of Pharmacy; 2017. (In Ukrainian).
37. Mukherji A, Dachraoui M, Baumert TF. Perturbation of the circadian clock and pathogenesis of NAFLD. Metabolism. 2020;111S:154337. PMID: 32795560. PMCID: PMC7613429. https://doi.org/10.1016/j.metabol.2020.154337
38. Avagimyan A, Popov S, Shalnova S. the pathophysiological basis of diabetic cardiomyopathy development. Curr Probl Cardiol. 2022;47(9):101156. PMID: 35192869. https://doi.org/10.1016/j.cpcardiol.2022.101156
39. Avagimyan A, Fogacci F, Pogosova N, et al. Diabetic cardiomyopathy: 2023 update by the International Multidisciplinary Board of Experts. Curr Probl Cardiol. 2024;49(1 Pt A):102052. PMID: 37640176. https://doi.org/10.1016/j.cpcardiol.2023.102052
40. Samuel VT, Shulman GI. Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases. Cell Metab. 2018;27(1):22–41. PMID: 28867301. PMCID: PMC5762395. https://doi.org/10.1016/j.cmet.2017.08.002
41. Saran AR, Dave S, Zarrinpar A. Circadian rhythms in the pathogenesis and treatment of fatty liver disease. Gastroenterology. 2020;158(7):1948–1966.e1. PMID: 32061597. PMCID: PMC7279714. https://doi.org/10.1053/j.gastro.2020.01.050
42. Chen P, Han Z, Yang P, Zhu L, Hua Z, Zhang J. Loss of clock gene mPer2 promotes liver fibrosis induced by carbon tetrachloride. Hepatol Res. 2010;40(11):1117–1127. PMID: 20880056. https://doi.org/10.1111/j.1872-034X.2010.00695.x
43. Tahara Y, Shibata S. Circadian rhythms of liver physiology and disease: experimental and clinical evidence. Nat Rev Gastroenterol Hepatol. 2016;13(4):217–226. PMID: 26907879. https://doi.org/10.1038/nrgastro.2016.8
44. Diallo AB, Coiffard B, Leone M, Mezouar S, Mege JL. For whom the clock ticks: clinical chronobiology for infectious diseases. Front Immunol. 2020;11:1457. PMID: 32733482. PMCID: PMC7363845. https://doi.org/10.3389/fimmu.2020.01457
45. Feillet C, van der Horst GT, Levi F, Rand DA, Delaunay F. Coupling between the circadian clock and cell cycle oscillators: implication for healthy cells and malignant growth. Front Neurol. 2015;6:96. PMID: 26029155. PMCID: PMC4426821. https://doi.org/10.3389/fneur.2015.00096
46. Lin YM, Chang JH, Yeh KT, et al. Disturbance of circadian gene expression in hepatocellular carcinoma. Mol Carcinog. 2008;47(12):925–933. PMID: 18444243. https://doi.org/10.1002/mc.20446
47. Yeh CT, Lu SC, Tseng IC, et al. Antisense overexpression of BMAL2 enhances cell proliferation. Oncogene. 2003;22(34):5306–5314. PMID: 12917632. https://doi.org/10.1038/sj.onc.1206674
48. Cui M, Sun J, Hou J, et al. The suppressor of cytokine signaling 2 (SOCS2) inhibits tumor metastasis in hepatocellular carcinoma. Tumour Biol. 2016;37(10):13521–13531. PMID: 27465557. https://doi.org/10.1007/s13277-016-5215-7
49. Lee JH, Sancar A. Circadian clock disruption improves the efficacy of chemotherapy through p73-mediated apoptosis. Proc Natl Acad Sci U S A. 2011;108(26):10668–10672. PMID: 21628572. PMCID: PMC3127903. https://doi.org/10.1073/pnas.1106284108
50. Kelleher FC, Rao A, Maguire A. Circadian molecular clocks and cancer. Cancer Lett. 2014;342(1):9–18. PMID: 24099911. https://doi.org/10.1016/j.canlet.2013.09.040
51. Filipski E, Subramanian P, Carrière J, Guettier C, Barbason H, Lévi F. Circadian disruption accelerates liver carcinogenesis in mice. Mutat Res. 2009;680(1–2):95–105. PMID: 19833225. https://doi.org/10.1016/j.mrgentox.2009.10.002
52. Jiang Y, Shen X, Fasae MB, et al. The expression and function of circadian rhythm genes in hepatocellular carcinoma. Oxid Med Cell Longev. 2021;2021:4044606. PMID: 34697563. PMCID: PMC8541861. https://doi.org/10.1155/2021/4044606
53. Zhao B, Lu J, Yin J, et al. A functional polymorphism in PER3 gene is associated with prognosis in hepatocellular carcinoma. Liver Int. 2012;32(9):1451–1459. PMID: 22809120. https://doi.org/10.1111/j.1478-3231.2012.02849.x
54. Kettner NM, Voicu H, Finegold MJ, et al. Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis. Cancer Cell. 2016;30(6):909–924. PMID: 27889186. PMCID: PMC5695235. https://doi.org/10.1016/j.ccell.2016.10.007
55. Matsuo T, Yamaguchi S, Mitsui S, Emi A, Shimoda F, Okamura H. Control mechanism of the circadian clock for timing of cell division in vivo. Science. 2003;302(5643):255–259. PMID: 12934012. https://doi.org/10.1126/science.1086271
56. Zou Y, Bao Q, Kumar S, Hu M, Wang GY, Dai G. Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration. PLoS One. 2012;7(2):e30675. PMID: 22319576. PMCID: PMC3272022. https://doi.org/10.1371/journal.pone.0030675
57. Chao HW, Doi M, Fustin JM, et al. Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway. Nat Commun. 2017;8(1):2238. PMID: 29269828. PMCID: PMC5740157. https://doi.org/10.1038/s41467-017-02207-7
58. Ozturk N, Ozturk D, Kavakli IH, Okyar A. Molecular aspects of circadian pharmacology and relevance for cancer chronotherapy. Int J Mol Sci. 2017;18(10):2168. PMID: 29039812. PMCID: PMC5666849. https://doi.org/10.3390/ijms18102168
59. Sadiq Z, Varghese E, Büsselberg D. Cisplatin’s dualeffect on the circadian clock triggers proliferation and apoptosis. Neurobiol Sleep Circadian Rhythms. 2020;9:100054. PMID: 33364523. PMCID: PMC7752721. https://doi.org/10.1016/j.nbscr.2020.100054
60. Yang SK, Zhang HR, Shi SP, et al. The role of mitochondria in systemic lupus erythematosus: a glimpse of various pathogenetic mechanisms. Curr Med Chem. 2020;27(20):3346–3361. PMID: 30479205. https://doi.org/10.2174/0929867326666181126165139
61. Llanos JM, Dumm CL, Nessi AC. Ultrastructure of STH cells of the pars distalis of hepatectomized mice. Z Zellforsch Mikrosk Anat. 1971;113(1):29–38. PMID: 5545215. https://doi.org/10.1007/BF00331199
62. Ryzhikov M, Eubanks A, Haspel JA. Measuring diurnal rhythms in autophagic and proteasomal flux. J Vis Exp. 2019;(151):10.3791/60133. PMID: 31609346. https://doi.org/10.3791/60133
63. Fedchenko T, Izmailova O, Shynkevych V, Shlykova O, Kaidashev I. PPAR-γ agonist pioglitazone restored mouse liver mRNA expression of clock genes and inflammation-related genes disrupted by reversed feeding. PPAR Res. 2022;2022:7537210. PMID: 35663475. PMCID: PMC9162826. https://doi.org/10.1155/2022/7537210
64. Sinturel F, Gerber A, Mauvoisin D, et al. Diurnal oscillations in liver mass and cell size accompany ribosome assembly cycles. Cell. 2017;169(4):651–663.e14. PMID: 28475894. PMCID: PMC5570523. https://doi.org/10.1016/j.cell.2017.04.015
65. Weger M, Weger BD, Gachon F. The mechanisms and physiological consequences of diurnal hepatic cell size fluctuations: a brief review. Cell Physiol Biochem. 2022;56(S2):1–11. PMID: 35032423. https://doi.org/10.33594/000000489
66. Shi H, Brown LM, Rahimian R. Sex/gender differences in metabolism and behavior: influence of sex chromosomes and hormones. Int J Endocrinol. 2015;2015:245949. PMID: 26491439. PMCID: PMC4600911. https://doi.org/10.1155/2015/245949
67. Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev. 2011;35(3):565–572. PMID: 20620164. PMCID: PMC3008499. https://doi.org/10.1016/j.neubiorev.2010.07.002
68. Zucker I, Beery AK. Males still dominate animal studies. Nature. 2010;465(7299):690. PMID: 20535186. https://doi.org/10.1038/465690a
69. Marcos RJPC. Age and Gender Influences on the Rat Liver Model: Quantitative Morphological Studies of Hepatic Stellate Cells, Hepatocytes and Kupffer Cells and of Related Functional Parameters. Dissertation. University of Porto; 2013.
70. Shan YS, Hsieh YH, Sy ED, Chiu NT, Lin PW. The influence of spleen size on liver regeneration after major hepatectomy in normal and early cirrhotic liver. Liver Int. 2005;25(1):96–100. PMID: 15698405. https://doi.org/10.1111/j.1478-3231.2005.01037.x
71. Klaassen CD, Aleksunes LM. Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol Rev. 2010;62(1):1–96. PMID: 20103563. PMCID: PMC2835398. https://doi.org/10.1124/pr.109.002014
72. Justo R, Boada J, Frontera M, Oliver J, Bermúdez J, Gianotti M. Gender dimorphism in rat liver mitochondrial oxidative metabolism and biogenesis. Am J Physiol Cell Physiol. 2005;289(2):C372–C378. PMID: 15800054. https://doi.org/10.1152/ajpcell.00035.2005
73. Lefebvre P, Staels B. Hepatic sexual dimorphism - implications for non-alcoholic fatty liver disease. Nat Rev Endocrinol. 2021;17(11):662–670. PMID: 34417588. https://doi.org/10.1038/s41574-021-00538-6
74. Leskanicova A, Chovancova O, Babincak M, et al. Sexual dimorphism in energy metabolism of Wistar rats using data analysis. Molecules. 2020;25(10):2353. PMID: 32443550. PMCID: PMC7287681. https://doi.org/10.3390/molecules25102353
75. Zheng D, Wang X, Antonson P, Gustafsson JÅ, Li Z. Genomics of sex hormone receptor signaling in hepatic sexual dimorphism. Mol Cell Endocrinol. 2018;471:33–41. PMID: 28554805. PMCID: PMC5702598. https://doi.org/10.1016/j.mce.2017.05.025
76. Bur IM, Cohen-Solal AM, Carmignac D, et al. The circadian clock components CRY1 and CRY2 are necessary to sustain sex dimorphism in mouse liver metabolism. J Biol Chem. 2009;284(14):9066–9073. PMID: 19211562. PMCID: PMC2666555. https://doi.org/10.1074/jbc.M808360200
77. Pinkhasov BB, Selyatinskaya VG, Astrakhantseva EL, Anufrienko EV. Circadian rhythms of carbohydrate metabolism in women with different types of obesity. Bull Exp Biol Med. 2016;161(3):323–326. PMID: 27492405. https://doi.org/10.1007/s10517-016-3406-2
78. Пинхасов Б.Б., Сорокин М.Ю., Янковская С.В., Михайлова Н.И., Селятицкая В.Г. Гендерные особенности циркадного ритма углеводного обмена. Сибирский научный медицинский журнал. 2021;41(2):85–91. https://doi.org/10.18699/ssmj20210212
79. Soares AF, Paz-Montoya J, Lei H, Moniatte M, Gruetter R. Sexual dimorphism in hepatic lipids is associated with the evolution of metabolic status in mice. NMR Biomed. 2017;30(10):10.1002/nbm.3761. Published correction appears in NMR Biomed. 2017 Dec;30(12). PMID: 28661066. https://doi.org/10.1002/nbm.3761
80. Tucci S, Flögel U, Spiekerkoetter U. Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT). Biochim Biophys Acta. 2015;1852(7):1442–1450. PMID: 25887160. https://doi.org/10.1016/j.bbadis.2015.04.009
81. Guillaumond F, Gréchez-Cassiau A, Subramaniam M, et al. Kruppel-like factor KLF10 is a link between the circadian clock and metabolism in liver. Mol Cell Biol. 2010;30(12):3059–3070. PMID: 20385766. PMCID: PMC2876690. https://doi.org/10.1128/MCB.01141-09
82. Pérez-Mendoza M, Rivera-Zavala JB, Rodríguez-Guadarrama AH, et al. Daily cycle in hepatic lipid metabolism in obese mice, Neotomodon alstoni: sex differences. Chronobiol Int. 2018;35(5):643–657. PMID: 29370528. https://doi.org/10.1080/07420528.2018.1424178
83. Xu YQ, Zhang D, Jin T, et al. Diurnal variation of hepatic antioxidant gene expression in mice. PLoS One. 2012;7(8):e44237. PMID: 22952936. PMCID: PMC3430632. https://doi.org/10.1371/journal.pone.0044237
Рецензия
Для цитирования:
Арешидзе Д.А., Кактурский Л.В. Циркадные ритмы печени и их половой диморфизм: современное состояние проблемы. Инновационная медицина Кубани. 2024;(2):108-114. https://doi.org/10.35401/2541-9897-2024-9-2-108-114
For citation:
Areshidze D.A., Kakturskiy L.V. Circadian Rhythms of the Liver and Their Sexual Dimorphism: Current State of the Problem. Innovative Medicine of Kuban. 2024;(2):108-114. https://doi.org/10.35401/2541-9897-2024-9-2-108-114
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