Diyabetik Kardiyomiyopati Sıçan Modelinde Oksitosin Etkilerinin Histolojik ve Biyokimyasal Olarak İncelenmesi

Year 2017, Volume: 44 Issue: 2, 135 - 143, 01.06.2017

Türker Çavuşoğlu Öznur Dilek Çiftçi Eylem Çağıltay Ayfer Meral İlker Kızıloğlu Serkan Gürgül Yiğit Uyanıkgil , Oytun Erbaş

https://doi.org/10.5798/dicletip.307933

Cited By: 1

Abstract

Amaç: Son yıllarda prevalansı hızla artan, çeşitli kardiyak
bozukluklara neden olan Diyabetes mellitus kronik metabolik bir hastalıktır.
Sedanter yaşam şekli ve beslenme alışkanlıklarındaki yanlışlıklara bağlı olarak
önemli bir sağlık problemi haline gelmiştir. Bu çalışmada, deneysel sıçan
diyabetik kardiyomiyopati modelinde hiperglisemi ile oluşturulmuş hücresel
hasar üzerinde oksitosin etkilerinin histolojik ve biyokimyasal olarak
incelenmesi amaçlanmıştır.

Yöntemler: On iki adet sıçanın intraperitoneal (i.p)
streptozosin enjeksiyonu ile diyabetik olmaları sağlandı. Sıçanların geri kalanına
(n=6) herhangi bir verilmedi. Çalışma kapsamına 250 mg/dl ve daha yüksek kan
şekeri düzeylerine sahip olan diyabetik kabul edilerek çalışmaya alındı. Daha
sonra, diyabetik hale getirilmiş olan sıçanlar (n=12) rastgele, 1 mL/kg salin
ile tedavi edilen diyabet grubu ve 28 gün boyunca 160 μg/kg/gün i.p oksitosin
ile tedavi edilen diyabet grubu olmak üzere 2 gruba ayrıldı. Hayvanlar 28 günün
sonunda sakrifiye edilip kalpten alınan kan ile biyokimyasal analizler, kalp
kasından da histopatolojik incelemeler yapıldı.

Bulgular: Diyabetik sıçanlarda oksitosin uygulaması ile
histolojik olarak kardiyomiyosit kalınlığının azaldığı, biyokimyasal olarak ise
TGF-β1 immünoekspresyonun, TGF-β, malondialdehit ve pentraxin-3 seviyelerinin
azaldığı gözlemlenmiştir.

Sonuç: Bu çalışmada elde edilen bulgular oksitosinin
diyabetik kardiyomiyopatide olumlu etkilerinin olabileceğini göstermektedir.

Keywords

Diyabetik kardiyomiyopati, oksitosin

References

• 1. Laakso M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999;48:937-42.
• 2. Rubler S, Dlugash J, Yuceoglu YZ, et al. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972;30:595-602.
• 3. Brownlee M. Negative consequences of glycation. Metabolism 2000;49:9-13.
• 4. Wolff SP, Jiang ZY, Hunt JV. Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 1991;10:339-52.
• 5. Cai L, Kang YJ. Oxidative stress and diabetic cardiomyopathy: a brief review. Cardiovasc Toxicol 2001;1:181-193.
• 6. Frustaci A, Kajstura J, Chimenti C, et al. Myocardial cell death in human diabetes. Circ Res 2000;87:1123-32.
• 7. Sharma AK, Srinivasan BP. Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes mellitus rats. Eur J Pharm Sci 2009;38:433-44.
• 8. van den Brom CE, Huisman MC, Vlasblom R, et al. Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography. Cardiovasc Diabetol 2009;8:39.
• 9. Chatham JC, Forder JR. A 13-C NMR study of glucose oxidation in the intact functioning rat heart following diyabetes-induced cardiomyopathy. J Mol Cell Cardiol 1993;10:1203-13.
• 10. Cosentino F, Eto M, De Paolis P, et al. High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: role of protein kinase C and reactive oxygen species. Circulation 2003;107:1017-23.
• 11. Camici GG, Schiavoni M, Francia P, et al. Genetic deletion of p66(Shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress. Proc Natl Acad Sci USA 2007;104:5217-22.
• 12. Bhimji S, Godin DV, McNeill JH. Myocardial ultrastructural changes in alloxan-induced diyabetes in rabbits. Acta Anat (Basel) 1986;125:195-200.
• 13. Erbaş O. Oksitosinin fizyolojik etkileri ve klinik uygulama alanları. Izm Univ Med J 2013;1:43-53.
• 14. Hayat SA, Patel B, Khattar RS, et al. Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clin Sci (Lond). 2004;107:539-57.
• 15. Avendano GF, Agarwal RK, Bashey RI, et al. Effects of glucose intolerance on myocardial function and collagen-linked glycation. Diabetes 1999;48:1443-7.
• 16. Eguchi K, Boden-Albala B, Jin ZZ, et al. Association between diabetesmellitus and left ventricular hypertrophy in a multiethnic population. Am J Cardiol 2008; 101:1787-91.
• 17. Wold LE, Ceylan-Isık AF, Fang CX, et al. Metallothionein alleviates cardiac dysfunction instreptozotocin-induced diabetes: role of Ca2+ cycling proteins, NADPH oxidase, poly (ADP-ribose) polymerase and myosin heavy chain isozyme. Free Radical Biol Med 2006;40:1419-29.
• 18. Nakamura K, Fushimi K, Kouchi H, et al. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-a and angiotensin II. Circulation 1998;98:794-9.
• 19. Gutkowska J, Jankowski M, Lambert C, et al. Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors inthe heart. Proc Natl Acad Sci USA 1997;94:11704-9.
• 20. Ondrejcakova M, Ravingerova T, Bakos J, et al. Oxytocin exerts protective effects on in vitro myocardial injury induced by ischemia and reperfusion. CanJ Physiol Pharmacol 2009;87:137-42.
• 21. Tsuchida K, Makita Z, Yamagishi S, et al. Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia 1999;42:579-88.
• 22. Agocha A, Hyeon-Woo L, Mahboubeh EW. Hypoxia regulates basal and induced DNA synthesis and collagen type I production in human cardiac fibroblasts: effects of TGFβ, thyroid hormone, angiotensin II and basic FGF. J Mol Cell Cardiol 1997;29:2233-44.
• 23. Brownlee M, Cerami A. The biochemistry of the complications of diabetes mellitus. Annu Rev Biochem 1981;50:385-432.
• 24. Wolff SP, Jiang ZY, Hunt JV. Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 1991;10:339-52.
• 25. Wojtczak L, Schonfeld P. Effect of fatty acids on energy coupling processes in mitochondria. Biochim Biophys Acta 1993;1183:41-57.
• 26. Griesmacher A, Kindhauser M, Andert SE, et al. Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus. Am J Med 1995;98:469-75.
• 27. Laaksonen DE, Atalay M, Niskanen L, et al. Increasedresting and exercise-induced oxidative stress in young IDDM men. Diabetes Care 1996;19:569-74.
• 28. Devasagayam TP, Boloor KK, Ramasarma T. Methods for estimating lipid peroxidation: an analysis of merits and demerits. Indian J Biochem Biophys 2003;40:300-8.
• 29. Tuğtepe H, Sener G, Bıyıklı NK, et al. The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept 2007;140:101-8.
• 30. Hekimoglu AT, Toprak G, Akkoc H, et al. Oxytocin ameliorates remote liver injury induced by renal ischemia-reperfusion in rats. Korean J Physiol Pharmacol 2013;17:169-73.
• 31. Mantovani A, Garlanda C, Bottazzi B. Pentraxin 3, a non-redundant soluble pattern recognition receptor involved in innate immunity. Vaccine 2003;21:43-7.
• 32. Alles VV, Bottazzi B, Peri G, et al. Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes. Blood 1994;84:3483-93.
• 33. Salio M, Chimenti S, De Angelis N, et al. Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction. Circulation 2008;117:1055-64.
• 34. İşeri SO, Şener G, Sağlam B, et al. Oxytocin ameliorates oxidative colonic inflammation by neutrophil-dependent mechanism. Peptide 2005;26:483-91.
• 35. Eckertova M, Ondrejcakova M, Krskova K, et al. Subchronic treatment of rats with oxytocin results in improved adipocyte differentiation and increased gene expression of factors involved in adipogenesis. Br J Pharmacol 2011;162:452-63.