Ferda HOSGORLER, Servet KIZILDAĞ, Başar KOÇ, Güven GÜVENDİ, Sevim KANDİŞ, Mehmet ATEŞ, Nazan UYSAL

Yaşlı Dişi Sıçanlarda Akut ve Kronik Stres Yanıtlarının Midede TNF-α ve IL-10 Düzeylerine Etkileri

Amaç: Stres karşısında enerji ve kan akımını gereken bölgelere yönlendiren Hipotalamus-Pitüiter-Adrenal (HPA) aksın yanıtları yaşlılarda bozulmaktadır. Mide, stres ve kortisol etkilerine oldukça duyarlıdır. Akut stres ve kronik stres farklı kortisol cevapları oluşturabilir. Çalışmanın amacı yaşlı dişi sıçanlarda akut ve kronik stresin mide inflamasyon belirteçleri üzerine etkisinin değerlendirilmesidir. Gereç ve Yöntem: 24-30 aylık dişi Sprague Dawley sıçanlar (n=18), kontrol, akut stres (60 dakikalık restraint stresi) ve kronik stres (14 gün tekrarlayan 60 dakikalık restraint stresi) gruplarında değerlendirildi. Stres sonrası serumda kortikosteron, mide dokularında TNF-α ve IL-10 düzeyleri ELISA yöntemi ile incelendi. Sonuçlar SPSS 24 programında One Way Anova ve post-hoc Tukey testi ile analiz edildi. Pearson korelasyon analiziyle kortikosteron düzeyleri ve sitokin düzeyleri arasındaki ilişki belirlendi, p<0,05 anlamlı kabul edildi. Bulgular: Akut stres grubunda kontrol grubuna göre serum kortikosteron düzeylerinin arttığı, kronik stres grubunda kontrole göre değişmediği görüldü. Mide TNF-α düzeylerinin akut ve kronik stres grubunda kontrole göre arttığı görüldü. Akut stres ve kontrol gruplarında kortikosteron ve TNF-α arasında pozitif korelasyon saptandı. Mide IL-10 düzeylerinde gruplar arası belirgin bir fark saptanmadı. Sonuç: Araştırmamızda yaşlı dişi sıçanlarda kronik stresin akut strese göre daha düşük kortikosteron yanıtı oluşturduğu ortaya koyulmuştur. Bu durum böbrek üstü bezinin glukokortikoid replasman yeteneğinin yaşlılarda yetersizliğiyle ilişkili olabilir. Tekrarlayan stresle akut inflamasyon bulgularının daha da artmaması, kronik strese karşı midenin adaptasyon geliştirme mekanizmalarını akla getirmiştir. Akut stresle ilişkili midedeki proinflamatuvar sitokin TNF-α düzeylerinin değişiminde kortikosteronun rolü olduğu ortaya konmuştur.

Anahtar Kelimeler:

yaşlı, mide, stres

Effects of Acute and Chronic Stress Responses on Gastric TNF-α and IL-10 Levels in Female Elderly Rats

Objective: The physiological responses of the hypothalamus-pituitary-adrenal (HPA) axis, which directs energy and blood flow to required regions against stress, are impaired in the elderly. Stomach is very sensitive to stress and cortisol effects. Acute and chronic stress can produce different cortisol responses. The aim of this study was to evaluate the effect of acute and chronic stress on gastric inflammation markers in elderly female rats. Materials and Methods: Sprague Dawley female rats (n = 18) aged 24-30 months were evaluated in the control, acute stress (60-minute restraint stress) and chronic stress (restraint stress for 14 day) groups. Following stress, serum corticosterone, TNF-α and IL-10 levels in gastric tissues were examined by ELISA method. Results were analyzed by One Way Anova and post-hoc Tukey test in SPSS 24 program. Pearson correlation analysis was used and p<0.05 was considered significant. Results: Serum corticosterone levels increased in the acute stress group but did not change in the chronic stress group compared to controls. Gastric TNF-α levels increased both in the acute and chronic stress group compared to controls. There was a positive correlation between corticosterone and TNF-α in acute stress and control groups. IL-10 levels did not change in groups. Conclusion: In elderly female rats, lower corticosterone response occurred with chronic stress. This may be related to insufficiency of glucocorticoid replacement ability of adrenal gland. Markers of acute inflammation did not increase further in chronic stress due to possible adaptation mechanisms of the stomach. Corticosterone caused changes in TNF-α levels, a proinflammatory cytokine in the stomach, during acute stress.

Keywords:

elderly, stomach, stress,

PDF

___

1. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science (New York, NY). 1997;278(5337):419-24.
2. Soreq L, Rose J, Soreq E, Hardy J, Trabzuni D, Cookson MR, et al. Major shifts in glial regional identity are a transcriptional hallmark of human brain aging. Cell Rep. 2017;18(2):557-70.
3. Buechel H, Popovic J, Staggs K, Anderson K, Thibault O, Blalock E. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging. Front Aging Neurosci. 2014;6(13).
4. Yang Y, Zhang X, Zhu Y, Dai Y, Liu T, Wang Y. Cognitive impairment in generalized anxiety disorder revealed by event-related potential N270. Neuropsychiatr Dis Treat. 2015;11:1405-11.
5. Mathews A. Why worry? The cognitive function of anxiety. Behav Res Ther. 1990;28(6):455-68.
6. Schneiderman N, Ironson G, Siegel SD. Stress and Health: Psychological, Behavioral, and Biological Determinants. Annu Rev Clin Psychol. 2005;1:607-28.
7. Ahn T, Bae CS, Yun C-H. Acute stress-induced changes in hormone and lipid levels in mouse plasma Veterinární Medicína. 2016;61:57-64.
8. Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev. 1986;7(3):284-301.
9. Gaffey AE, Bergeman CS, Clark LA, Wirth MM. Aging and the HPA axis: Stress and resilience in older adults. Neurosci Biobehav Rev. 2016;68:928-45.
10. Goncharova ND, Oganyan TE. Age-related differences in stress responsiveness of the hypothalamic-pituitary-adrenal axis of nonhuman primates with various types of adaptive behavior. Gen Comp Endocrinol. 2018;258:163-72.
11. Buechel HM, Popovic J, Staggs K, Anderson KL, Thibault O, Blalock EM. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging. Front Aging Neurosci. 2014;6:13-.
12. Ahluwalia A, Jones MK, Hoa N, Zhu E, Brzozowski T, Tarnawski AS. Reduced NGF in gastric endothelial cells is one of the main causes of impaired angiogenesis in aging gastric mucosa. Cell Mol Gastroenterol Hepatol. 2018;6(2):199-213.
13. Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011;62(6):591-9.
14. Collins SM. Stress and the Gastrointestinal Tract IV. Modulation of intestinal inflammation by stress: basic mechanisms and clinical relevance. Am J Physiol Gastrointest Liver Physiol. 2001;280(3):G315-8.
15. Dong J, Li J, Cui L, Wang Y, Lin J, Qu Y, et al. Cortisol modulates inflammatory responses in LPS-stimulated RAW264.7 cells via the NF-κB and MAPK pathways. BMC Vet Res. 2018;14(1):30.
16. Selye H, Jean P, Cantin M. Prevention by stress and cortisol of gastric ulcers normally produced by 48/80. Proc Soc Exp Biol Med. 1960;103(2):444-6.
17. Robert A, Nezamis JE. Effect of cortisol on gastric ulcers of the Shay rat. Proc Soc Exp Biol Med.1958;98(1):9-12.
18. Roelfsema F, van Heemst D, Iranmanesh A, Takahashi P, Yang R, Veldhuis JD. Impact of age, sex and body mass index on cortisol secretion in 143 healthy adults. Endocr Connect. 2017;6(7):500-9.
19. Campos AC, Fogaca MV, Aguiar DC, Guimaraes FS. Animal models of anxiety disorders and stress. Braz J Pschiatry. 2013;35 Suppl 2:S101-11.
20. Reis DG, Scopinho AA, Guimarães FS, Corrêa FMA, Resstel LBM. Behavioral and autonomic responses to acute restraint stress are segregated within the lateral septal area of rats. PloS one. 2011;6(8):e23171-e.
21. Brodish A, Odio M. Age-dependent effects of chronic stress on ACTH and corticosterone responses to an acute novel stress. Neuroendocrinology. 1989;49(5):496-501.
22. Oh HJ, Song M, Kim YK, Bae JR, Cha SY, Bae JY, et al. Age-related decrease in stress responsiveness and proactive coping in male mice. Front Aging Neurosci. 2018;10:128.
23. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci U S A. 2010;107(6): 2669-74.
24. Tracey KJ. The inflammatory reflex. Nature. 2002;420(6917):853-9.
25. Busillo JM, Cidlowski JA. The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends Endocrinol Metab. 2013;24(3):109-19.
26. Ayroldi E, Cannarile L, Migliorati G, Nocentini G, Delfino DV, Riccardi C. Mechanisms of the anti-inflammatory effects of glucocorticoids: genomic and nongenomic interference with MAPK signaling pathways. FASEB J. 2012;26(12):4805-20.
27. Cruz-Topete D, Cidlowski JA. One hormone, two actions: anti- and pro-inflammatory effects of glucocorticoids. Neuroimmunomodulation. 2015;22(1-2):20-32.
28. Padgett DA, Glaser R. How stress influences the immune response. Trends Immunol. 2003;24(8):444-8.
29. Zhu L, Shi T, Zhong C, Wang Y, Chang M, Liu X. IL-10 and IL-10 Receptor mutations in very early onset inflammatory bowel disease. Gastroenterology Res. 2017;10(2):65-9.
30. Tian R, Hou G, Li D, Yuan T-F. A possible change process of inflammatory cytokines in the prolonged chronic stress and its ultimate implications for health. ScientificWorldJournal. 2014;2014:8.
31. Ochi M, Tominaga K, Tanaka F, Tanigawa T, Shiba M, Watanabe T, et al. Effect of chronic stress on gastric emptying and plasma ghrelin levels in rats. Life Sci. 2008;82(15):862-8.
32. Mikhail AA. Effects of acute and chronic stress situations on stomach acidity in rats. J Comp Physiol Psychol. 1971;74(1, Pt.1):23-7.
33. McLean CP, Asnaani A, Litz BT, Hofmann SG. Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. J Psychiatr Res. 2011;45(8):1027-35.
34. Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin J-M, Jones JF, et al. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. J Clin Endocrinol Metab. 2008;93(3):703-9.
35. Pruessner JC, Wolf OT, Hellhammer DH, Buske-Kirschbaum A, von Auer K, Jobst S, et al. Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity. Life Sci. 1997;61(26):2539-49.
36. Seeman TE, Singer B, Wilkinson CW, Bruce M. Gender differences in age-related changes in HPA axis reactivity. Psychoneuroendocrinology. 2001;26(3):225-40.