Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65155710.31857/S086981392306002XWGYLZJEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИComparative Analysis of the Fibrosis Factors Expression in the Heart Tissue of Sprague-Dawley and Wistar Rats during Development of Chronic Renal FailureСравнительный анализ экспрессии факторов фиброза в сердечной ткани крыс Sprague-Dawley и Wistar при развитии хронической почечной недостаточностиAgalakovaN. I.АгалаковаН. И.irinaromanova@mail.ruMikhailovaE. V.МихайловаЕ. В.irinaromanova@mail.ruPiankovА. А.ПьянковА. А.irinaromanova@mail.ruNadeiO. V.НадейО. В.irinaromanova@mail.ruErshovI. А.ЕршовИ. А.irinaromanova@mail.ruGalagudzaM. V.ГалагудзаМ. М.irinaromanova@mail.ruBagrovA. Y.БагровА. Я.irinaromanova@mail.ruRomanovaI. V.РомановаИ. В.irinaromanova@mail.ruSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesИнститут эволюционной физиологии и биохимии им. И.М. Сеченова Российской академии наукPeter the Great Saint-Petersburg Polytechnic UniversityСанкт-Петербургский политехнический университет Петра ВеликогоInstitute of Experimental Medicine, Almazov National Medical Research Center, Ministry of the Health of the Russian FederationИнститут экспериментальной медицины НМИЦ им. В.А. Алмазова Минздрава РоссииPadakonn Pharma01062023109673774801022025Copyright ©; 2023, Н.И. Агалакова, Е.В. Михайлова, А.А. Пьянков, О.В. Надей, И.А. Ершов, М.М. Галагудза, А.Я. Багров, И.В. РомановаCopyright ©; 2023, Н.И. Агалакова, Е.В. Михайлова, А.А. Пьянков, О.В. Надей, И.А. Ершов, М.М. Галагудза, А.Я. Багров, И.В. Романова2023Н.И. Агалакова, Е.В. Михайлова, А.А. Пьянков, О.В. Надей, И.А. Ершов, М.М. Галагудза, А.Я. Багров, И.В. РомановаН.И. Агалакова, Е.В. Михайлова, А.А. Пьянков, О.В. Надей, И.А. Ершов, М.М. Галагудза, А.Я. Багров, И.В. Романоваhttps://journals.eco-vector.com/0869-8139/article/view/651557

The severity of the development of uremic cardiomyopathy (UC) and fibrosis of cardiac tissue at chronic renal failure (CRF) was compared in the model experiments on male Sprague-Dawley and Wistar rats of the SPF category. To induce CRF in rats, subtotal nephrectomy (NE) was performed on the left, and after 2 weeks, total nephrectomy on the right. Sham-operated (Sham) animals served as controls. 4 weeks after the second surgery, blood pressure (BP) was measured in animals, and the expression of fibrotic factors (transcription factor Fli1, pro-collagen-I, collagen-I and collagen-IV) in the tissues of heart left ventricle was evaluated by real-time PCR and immunoblotting. After NE, Sprague-Dawley rats exhibited a significant increase in systolic blood pressure and left ventricular hypertrophy. In Wistar rats, the difference in BP between NE and Sham animals was smaller, and the ratio of left ventricular mass to body weight did not change. Experimental CRF in Sprague-Dawley rats was accompanied by a 1.5–2.5-fold suppression of the Fli1 gene expression and a decrease in the content of Fli1 protein in the cardiac tissue, while no significant differences were observed in Wistar rats. The levels of pro-collagen-I and collagen-I in the heart of rats of both lines did not change either at the levels of transcription or translation. Such difference in development of pathological processes indicates ineffectiveness of applied NE scheme for induction of UC and investigation of pro-fibrotic processes in Wistar rats.

Проведено сравнение степени развития уремической кардиомиопатии и фиброза сердечной ткани при хронической почечной недостаточности в модельных экспериментах на самцах крыс Sprague-Dawley и Wistar категории SPF. Для индукции ХПН у крыс проводили субтотальную нефрэктомию слева, а через 2 нед. – тотальную нефрэктомию справа. Контролем служили ложнооперированные животные. Через 4 нед. после второй операции у животных измеряли артериальное давление, а в тканях левого желудочка сердца методами ПЦР в реальном времени и иммуноблоттинга оценивали экспрессию факторов фиброза (транскрипционного фактора Fli1, проколлагена-I, коллагена-I и коллагена-IV). После нефрэктомии у крыс Sprague-Dawley выявлено значительное повышение систолического артериального давления и гипертрофия левого желудочка сердца. У крыс Wistar разница артериального давления между нефрэктомированными и ложнооперированными животными была меньше, а отношение массы левого желудочка к массе тела не изменилось. Экспериментальная хроническая почечная недостаточность у крыс Sprague-Dawley сопровождалась 1.5–2.5-кратным подавлением экспрессии гена Fli1 и снижением содержания белка Fli1 в ткани сердца, в то время как у крыс Wistar достоверных различий не наблюдалось. Уровни проколлагена-I и коллагена-I в сердце крыс обеих линий не изменялись ни на уровне транскрипции, ни на уровне трансляции. Такая разница в развитии патологических процессов в ткани сердца животных двух линий свидетельствует о неэффективности примененной схемы нефрэктомии для индукции уремической кардиомиопатии и изучения про-фибротических механизмов у крыс Wistar.

renal failurenephrectomyheartfibrosisFli1почечная недостаточностьнефрэктомиясердцефиброзFli1Garikapati K, Goh D, Khanna S, Echampati K (2021) Uraemic Cardiomyopathy: A Review of Current Literature. Clin Med Insights Cardiol 15: 1179546821998347. https://doi.org/10.1177/1179546821998347Patel N, Yaqoob MM, Aksentijevic D (2022) Cardiac metabolic remodelling in chronic kidney disease. Nat Rev Nephrol 18(8): 524–537. https://doi.org/10.1038/s41581-022-00576-xLaw JP, Pickup L, Pavlovic D, Townend JN, Ferro CJ (2023) Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations. J Hum Hypertens 37(1): 1–19. https://doi.org/10.1038/s41371-022-00751-4Adam RJ, Williams AC, Kriegel AJ (2022) Comparison of the surgical resection and infarct 5/6 nephrectomy rat models of chronic kidney disease. Am J Physiol Renal Physiol 322(6): F639–F654. https://doi.org/10.1152/ajprenal.00398.2021Kennedy DJ, Vetteth S, Periyasamy SM, Kanj M, Fedorova L, Khouri S, Kahaleh MB, Xie Z, Malhotra D, Kolodkin NI, Lakatta EG, Fedorova OV, Bagrov AY Shapiro JI (2006) Central role for the cardiotonic steroid marinobufagenin in the pathogenesis of experimental uremic cardiomyopathy. Hypertension 47: 488–495. https://doi.org/10.1161/01.HYP.0000202594.82271.92Elkareh, J, Kennedy DJ, Yashaswi B, Vetteth S, Shidyak A, Kim EG, Smaili S, Periyasamy SM, Hariri IM, Fedorova L, Liu J, Wu L, Kahaleh MB, Xie Z, Malhotra D, Fedorova OV, Kashkin VA, Bagrov AY, Shapiro JI (2007) Marinobufagenin stimulates fibroblast collagen production and causes fibrosis in experimental uremic cardiomyopathy. Hypertension 49(1): 215–224. https://doi.org/10.1161/01.HYP.0000252409.36927.05Haller ST, Kennedy DJ, Shidyak A, Budny GV, Malhotra D, Fedorova OV, Shapiro JI, Bagrov AY (2012) Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure. Am J Hypertens 25(6): 690–696. https://doi.org/10.1038/ajh.2012.17Elkareh J, Periyasamy SM, Shidyak A, Vetteth S, Schroeder J, Raju V, Hariri IM, El-Okdi N, Gupta S, Fedorova L, Liu J, Fedorova OV, Kahaleh MB, Xie Z, Malhotra D, Watson DK, Bagrov AY, Shapiro JI (2009) Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. Am J Physiol Renal Physiol 296(5): F1219–F1226. https://doi.org/10.1152/ajprenal.90710.2008Fleck C, Appenroth D, Jonas P, Koch M, Kundt G, Nizze H, Stein G (2006) Suitability of 5/6 nephrectomy (5/6NX) for the induction of interstitial renal fibrosis in rats – pinfluence of sex, strain, and surgical procedure. Exp Toxicol Pathol 57(3): 195–205. https://doi.org/10.1016/j.etp.2005.09.005Mikhailova EV, Romanova IV, Bagrov AY, Agalakova NI (2023) Fli1 and Tissue Fibrosis in Various Diseases. Int J Mol Sci 24(3): 1881. https://doi.org/10.3390/ijms24031881Agalakova NI, Grigorova Y, Ershov I, Reznik VA, Mikhailova EV, Nadei OV, Samuilovskaya L, Romanova LA, Adair CD, Romanova IV, Bagrov A (2022) Canrenone restores vasorelaxation impaired by marinobufagenin in human preeclampsia. Int J Mol Sci 23: 3336. https://doi.org/10.3390/ijms23063336Marques C, Meireles M, Norberto S, Leite J, Freitas J, Pestana D, Faria A, Conceição Calhau C (2016) High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat. Adipocyte 5(1): 11–21. https://doi.org/10.1080/21623945.2015.1061723Kühn ER, Bellon K, Huybrechts L, Heyns W (1983) Endocrine differences between the Wistar and Sprague-Dawley laboratory rat: influence of cold adaptation. Horm Metab Res 15(10): 491–498. https://doi.org/10.1055/s-2007-1018767Garg R, Heinzle E, Noor F (2018) Hepatocytes of Wistar and Sprague Dawley rats differ significantly in their central metabolism. J Cell Biochem 119(1): 909–917. https://doi.org/10.1002/jcb.26255Fujino H, Nakagawa M, Nishijima S, Okamoto N, Hanato T, Watanabe N, Shirai T, Kamiya H, Takeuchi Y (2005) Morphological differences in cardiovascular anomalies induced by bis-diamine between Sprague–Dawley and Wistar rats. Congenit Anom (Kyoto) 45: 52–58. https://doi.org/10.1111/j.1741-4520.2005.00063.xBazilio DS, Rodrigues KL, Moraes DJA, Machado BH (2021) Distinct cardiovascular and respiratory responses to short-term sustained hypoxia in juvenile Sprague Dawley and Wistar Hannover rats. Auton Neurosci 230: 102746. https://doi.org/10.1016/j.autneu.2020.102746Snow JB, Kanagy NL, Walker BR, Resta TC (2009) Rat Strain Differences in Pulmonary Artery Smooth Muscle Ca2+ Entry Following Chronic Hypoxia. Microcirculation 16(7): 603–614. https://doi.org/10.1080/10739680903114268Svoboda J, Litvinec A, Kala D, Pošusta A, Vávrová L, Jiruška P, Otáhal J (2019) Strain differences in intraluminal thread model of middle cerebral artery occlusion in rats. Physiol Res 68(1): 37–48. https://doi.org/10.33549/physiolres.933958Kunze A, Zierath D, Drogomiretskiy O, Becker K (2014) Variation in behavioral deficits and patterns of recovery after stroke among different rat strains. Transl Stroke Res 5(5): 569–576. https://doi.org/10.1007/s12975-014-0337-yRaman RN, Pivetti CD, Ramsamooj R, Matthews DL, Demos SG, Troppmann C (2011) Factors influencing rat survival in a warm renal ischemia model: time to adapt the protocols. Transplant Proc 43(5): 1511–1514. https://doi.org/10.1016/j.transproceed.2011.01.177Bidani AK, Mitchell KD, Schwartz MM, Navar LG, Lewis EJ (1990) Absence of glomerular injury or nephron loss in a normotensive rat remnant kidney model. Kidney Int 38: 28–38. https://doi.org/10.1038/ki.1990.163Appenroth D, Lupp A, Kriegsmann J, Sawall S, Splinther J, Sommer M, Stein G, Fleck C (2001) Temporary warm ischaemia, 5/6 nephrectomy and single uranyl nitrate administration–comparison of three models intended to cause renal fibrosis in rats. Exp Toxicol Pathol 53(4): 316–324. https://doi.org/10.1078/0940-2993-00197Saracyn M, Czarzasta K, Brytan M, Murawski P, Lewicki S, Ząbkowski T, Zdanowski R, Cudnoch-Jędrzejewska A, Kamiński GW, Wańkowicz Z (2017) Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental Model of 5/6 Nephrectomy. Med Sci Monit 23: 4865–4873. https://doi.org/10.12659/msm.903820Erdely A, Freshour G, Tain YL, Engels K, Baylis C (2007) DOCA/NaCl-induced chronic kidney disease: a comparison of renal nitric oxide production in resistant and susceptible rat strains. Am J Physiol Renal Physiol 292(1): F192–F196. https://doi.org/10.1152/ajprenal.00146.2006Drábková N, Hojná S, Zicha J, Vaněčková I (2020) Contribution of selected vasoactive systems to blood pressure regulation in two models of chronic kidney disease. Physiol Res 69(3): 405–414. https://doi.org/10.33549/physiolres.934392de Oliveira MG, Nadruz W Jr, Mónica FZ (2022) Endothelial and vascular smooth muscle dysfunction in hypertension. Biochem Pharmacol 205: 115263. https://doi.org/10.1016/j.bcp.2022.115263Martínez-Díaz I, Martos N, Llorens-Cebrià C, Álvarez FJ, Bedard PW, Vergara A, Jacobs-Cachá C, Soler MJ (2023) Endothelin receptor antagonists in kidney disease. Int J Mol Sci 24(4): 3427. https://doi.org/10.3390/ijms24043427Podyacheva EY, Shmakova TV, Andreeva DD, Toropov RI, Cheburkin YV, Danilchuk MS, Martynov MO, Toropova YG (2023) Molecular markers profile of fibrosis in rats exposed to different doses of doxorubicin. J Evol Biochem Physiol 59(2): 359–368. https://doi.org/10.1134/S0022093023020059