Электрокардиографические изменения у крыс с метаболическим синдромом и сахарным диабетом 2 типа

   Нарушения функций сердечно-сосудистой системы при метаболическом синдроме (МС) и сахарном диабете типа 2 (СД2) в экспериментальных работах изучены недостаточно, а данные об изменениях параметров ЭКГ, в том числе на моделях МС и СД2 у грызунов, противоречивы и неоднозначны.

   Цель исследования – изучить показатели ЭКГ на моделях МС и СД2 и выявить возможные корреляции между нарушением толерантности к глюкозе и выраженностью изменений параметров ЭКГ.

   Материал и методы. В экспериментах использовали самцов крыс Wistar. МС индуцировали высокожировой диетой (ВЖД) продолжительностью 17 недель, СД2 вызывали комбинацией ВЖД и инъекции стрептозотоцина (ВЖД+СТЗ): 11 недель ВЖД с последующим введением стрептозотоцина и продолжением ВЖД еще в течение 6 недель. Контрольные животные содержались на стандартной диете.

   Результаты. Глюкозотолерантный тест подтвердил развитие нарушенной толерантности к глюкозе до преддиабетического уровня у группы ВЖД и до диабетического уровня у группы ВЖД+СТЗ. Изменения в ЭКГ обнаружены только в группе ВЖД+СТЗ: показано статистически значимое (по сравнению с контрольной группой и группой ВЖД) увеличение амплитуды и площади Т зубца на ЭКГ.

   Заключение. Выраженные нарушения ЭКГ развиваются только при моделировании СД2, но не МС.

1. Henning R.J. Type-2 diabetes mellitus and cardiovascular disease. Future Cardiol. 2018;14(6):491-509. https://doi.org/10.2217/fca-2018-0045

2. Kanchi S., Sharma D. Diabetes and its effects: statistics and biosensors. J. Environ. Anal. Chem. 2015;02:e111. https://doi.org/10.4172/2380-2391.1000e111

3. Rodríguez-Correa E., González-Pérez I., Clavel-Pérez P.I., Contreras-Vargas Y., Carvajal K. Biochemical and nutritional overview of diet-induced metabolic syndrome models in rats: what is the best choice? Nutr. Diabetes. 2020;10(1):1-15. https://doi.org/10.1038/s41387-020-0127-4

4. Stern S., Sclarowsky S. The ECG in diabetes mellitus. Circulation. 2009;120(16):1633-1636. https://doi.org/10.1161/CIRCULATIONAHA.109.897496

5. de Artiñano A.A., Castro M.M. Experimental rat models to study the metabolic syndrome. Br. J. Nutr. 2009;102(9):1246-1253. https://doi.org/10.1017/S0007114509990729

6. Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J. Diabetes Investig. 2014;5(4):349-358. https://doi.org/10.1111/jdi.12235

7. Afolabi O.A., Alabi B.A., Oluranti O. Diet-induced insulin resistance altered cardiac GLUT4 and FATP/CD36 expression in rats. Beni-Suef Univ. J. Basic Appl. Sci. 2022;11(1):131. https://doi.org/10.1186/s43088-022-00312-1

8. Apaijai N., Pintana H., Chattipakorn S.C., Chattipakorn N. Cardioprotective effects of metformin and vildagliptin in adult rats with insulin resistance induced by a high-fat diet. Endocrinology. 2012;153(8):3878-3885. https://doi.org/10.1210/en.2012-1262

9. Abbas A.M., Sakr H.F. Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet. J. Physiol. Biochem. 2013;69(4):737-750. https://doi.org/10.1007/s13105-013-0250-y

10. Apaijai N., Arinno A., Palee S., Pratchayasakul W., Kerdphoo S., Jaiwongkam T., Chunchai T., Chattipakorn S.C., Chattipakorn N. High-saturated fat high-sugar diet accelerates left-ventricular dysfunction faster than high-saturated fat diet alone via increasing oxidative stress and apoptosis in obese-insulin resistant rats. Mol. Nutr. Food Res. 2019;63(2):1800729. https://doi.org/10.1002/mnfr.201800729

11. Bai Y., Su Z., Sun H., Zhao W., Chen X., Hang P., Zhu W., Du Z. Aloe-emodin relieves high-fat diet induced QT prolongation via MiR-1 Inhibition and IK1 up-regulation in rats. Cell. Physiol. Biochem. 2017;43(5):1961-1973. https://doi.org/10.1159/000484120

12. Gupta C., Omanwar S., Bubber P., Saidullah B. ECG alterations precedes cardiac hypertrophy in rat model of diabetes. Open Access. J. Toxicol. 2018;2(5):555598. https://doi.org/10.19080/OAJT.2018.02.555598

13. Zayas-Arrabal J., Alquiza A., Tuncay E., Turan B., Gallego M., Casis O. Molecular and electrophysiological role of diabetes-associated circulating inflammatory factors in cardiac arrhythmia remodeling in a metabolic-induced model of type 2 diabetic rat. Int. J. Mol. Sci. 2021;22(13):6827. https://doi.org/10.3390/ijms22136827

14. Ai J., Yan X., Zhao L., Lu Y., Liang F., Cai B., Li G., Lu Y., Yang B. The protective effect of daming capsule on heart function in streptozocin-induced diabetic rats with hyperlipidemia. Biol. Pharm. Bull. 2009;32(8):1354-1358. https://doi.org/10.1248/bpb.32.1354

15. Farrag E.A.E., Hammad M.O., Safwat S.M., Hamed S., Hellal D. Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway. Sci. Rep. 2023;13(1):11043. https://doi.org/10.1038/s41598-023-37678-w

16. Zhao T., Chen H., Xu F., Wang J., Liu Y., Xing X., Guo L., Zhang M., Lu Q. Liraglutide alleviates cardiac fibrosis through inhibiting P4hα-1 expression in STZ-induced diabetic cardiomyopathy. Acta Biochim. Biophys. Sin. (Shanghai). 2019;51(3):293-300. https://doi.org/10.1093/abbs/gmy177

17. Mostafa A., Samir S., Mahdi M. Effects of abscisic acid on the diabetic changes in rat myocardium. Bull. Egyptian Soc. Physiol. Sci. 2019;39(1):1-16. https://doi.org/10.21608/besps.2018.4308.1003

18. Löscher W., Cramer S., Ebert U. Differences in kindling development in seven outbred and inbred rat strains. Exp. Neurol. 1998;154(2):551-559. https://doi.org/10.1006/exnr.1998.6948

19. Bakhtyukov A.A., Derkach K.V., Sorokoumov V.N., Stepochkina A.M., Romanova I.V., Morina I.Y., Zakharova I.O., Bayunova L.V., Shpakov A.O. The effects of separate and combined treatment of male rats with type 2 diabetes with metformin and orthosteric and allosteric agonists of luteinizing hormone receptor on steroidogenesis and spermatogenesis. Int. J. Mol. Sci. 2021;23(1):198. https://doi.org/10.3390/ijms23010198

20. Derkach K.V., Bondareva V.M., Chistyakova O.V., Berstein L.M., Shpakov A.O. The effect of long-term intranasal serotonin treatment on metabolic parameters and hormonal signaling in rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes. Int. J. Endocrinol. 2015;2015:245459. https://doi.org/10.1155/2015/245459

21. Kuznetsova L.A., Derkach K.V., Sharova T.S., Bondareva V.M., Shpakov A.O. Effect of long-term L-thyroxine treatment on the activity of NO-synthases in tissues of rats with obesity induced by high-fat diet. J. Evol. Biochem. Physiol. 2015;51(6):485-494. https://doi.org/10.1134/S0022093015060058

22. Robins S.J., Rubins H.B., Faas F.H., Schaefer E.J., Elam M.B., Anderson J.W., Collins D., Veterans Affairs HDL Intervention Trial (VA-HIT). Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care. 2003;26(5):1513-1517. https://doi.org/10.2337/diacare.26.5.1513

23. Guembe M.J., Fernandez-Lazaro C.I., Sayon-Orea C., Toledo E., Moreno-Iribas C.; RIVANA Study Investigators. Risk for cardiovascular disease associated with metabolic syndrome and its components: a 13-year prospective study in the RIVANA cohort. Cardiovasc. Diabetol. 2020;19(1):195. https://doi.org/10.1186/s12933-020-01166-6

24. James D.E., Stöckli J., Birnbaum M.J. The aetiology and molecular landscape of insulin resistance. Nat. Rev. Mol. Cell Biol. 2021;22(11):751-771. https://doi.org/10.1038/s41580-021-00390-6

25. Kazlauskienė L., Butnorienė J., Norkus A. Metabolic syndrome related to cardiovascular events in a 10-year prospective study. Diabetol. Metab. Syndr. 2015;7:102. https://doi.org/10.1186/s13098-015-0096-2

26. Andrikopoulos S., Blair A.R., Deluca N., Fam B.C., Proietto J. Evaluating the glucose tolerance test in mice. Am. J. Physiol-Endocrinol. Metab. 2008;295(6):E1323-E1332. https://doi.org/10.1152/ajpendo.90617.2008

27. Bianchi C., Miccoli R., Trombetta M., Giorgino F., Frontoni S., Faloia E., Marchesini G., Dolci M.A., Cavalot F., Cavallo G., … GENFIEV Investigators. Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: The GENFIEV Study. J. Clin. Endocrinol. Metab. 2013;98(5):2100-2105. https://doi.org/10.1210/jc.2012-3971

28. Meigs J.B., Williams K., Sullivan L.M., Hunt K.J., Haffner S.M., Stern M.P., González Villalpando C., Perhanidis J.S., Nathan D.M., D’Agostino R.B. Jr., D’Agostino R.B. Sr., Wilson P.W.F. Using metabolic syndrome traits for efficient detection of impaired glucose tolerance. Diabetes Care. 2004;27(6):1417-1426. https://doi.org/10.2337/diacare.27.6.1417

29. Murakami M., Niwa H., Kushikata T., Watanabe H., Hirota K., Ono K., Ohba T. Inhalation anesthesia is preferable for recording rat cardiac function using an electrocardiogram. Biol. Pharm. Bull. 2014;37(5):834-839. https://doi.org/10.1248/bpb.b14-00012

30. Svorc P., Svorc P. Jr. General anesthesia and electrocardiographic parameters in vivo experiments involving rats. Physiol. Res. 2022;71(2):177-192. https://doi.org/10.33549/physiolres.934848

31. Marques C., Meireles M., Norberto S., Leite J., Freitas J., Pestana D., Faria A., Calhau C. High-fat diet-induced obesity rat model: a comparison between Wistar and Sprague-Dawley rat. Adipocyte. 2015;5(1):11-21. https://doi.org/10.1080/21623945.2015.1061723

32. Udomkasemsab A., Prangthip P. High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats. Clin. Investig. Arterioscler. 2019;31(2):56-62. https://doi.org/10.1016/j.arteri.2018.09.004

33. Shiou Y.L., Huang I.C., Lin H.T., Lee H.C. High fat diet aggravates atrial and ventricular remodeling of hypertensive heart disease in aging rats. J. Formos Med. Assoc. 2018;117(7):621-631. https://doi.org/10.1016/j.jfma.2017.08.008

34. Casis O., Gallego M., Iriarte M, Sánchez-Chapula J.A. Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle. Diabetologia. 2000;43(1):101-109. https://doi.org/10.1007/s001250050013

35. Shimoni Y., Ewart H.S., Severson D. Type I and II models of diabetes produce different modifications of K+ currents in rat heart: role of insulin. J. Physiol. 1998;507(Pt 2):485-496. https://doi.org/10.1111/j.1469-7793.1998.485bt.x

36. Ceasovschih A., Șorodoc V., Covantsev S., Balta A., Uzokov J., Kaiser S.E., Almaghraby A., Lionte C., Stătescu C., Sascău R.A., … Șorodoc L. Electrocardiogram features in non-cardiac diseases: from mechanisms to practical aspects. J. Multidiscip. Healthc. 2024;17:1695-1719. https://doi.org/10.2147/JMDH.S445549

37. Liamis G., Liberopoulos E., Barkas F., Elisaf M. Diabetes mellitus and electrolyte disorders. World J. Clin. Cases. 2014;2(10):488-496. https://doi.org/10.12998/wjcc.v2.i10.488

38. Bukhari H.A., Palmieri F., Ramírez J., Laguna P., Ruiz J.E., Ferreira D., Potse M., Sánchez C., Pueyo E. Characterization of T wave amplitude, duration and morphology changes during hemodialysis: Relationship with serum electrolyte levels and heart rate. IEEE Trans. Biomed. Eng. 2021;68(8):2467-2478. https://doi.org/10.1109/TBME.2020.3043844

39. Zou S., Zhang Q., Gao S., Luo M., Gan X, Liang K. Electrocardiogram manifestations of hyponatraemia. Cardiovasc. J. Afr. 2022;33(2):98-100. https://doi.org/10.5830/CVJA-2021-036