Publication: Cinsiyetin, hormonal durumun ve östrojen reseptörlerinin sıçanlarda stres ile oluşturulan mide ülserindeki etkilerinin araştırılması
Abstract
Amaç: Stres-ilişkili mukoza hasarı, yoğun bakım ünitesinde yatan hastalarda sıklıkla görülmektedir ve insidansı premenopozal kadınlarda erkeklere göre daha düşüktür. Bu tez çalışmasında, sıçanlarda psikolojik strese bağlı gelişen ülser modelinde (suda kısıtlama, WIRS) östrojen (E2) ve östrojen reseptörlerinin (ER) koruyucu etkilerinin mekanizmalarının aydınlatılması amaçlanmıştır. Gereç ve Yöntem: Erkek, dişi veya 8 hafta önce bilateral overektomi (OVX) yapılmış dişi sıçanlara 6 saat boyunca WIRS uygulanırken kontrol gruplarındaki sıçanlar sadece aç bırakıldılar. WIRS uygulamadan önceki 3 gün subkütan olarak E2, ER antagonistleri, ER agonistleri ya da taşıyıcı uygulandı. Midede kan akımı, mikroskopik ve makroskopik hasar skoru, PGE2 düzeyi, oksidan stres parametreleri, serumda inflamatuvar sitokinler, kortikosteron ve ACTH ölçüldü. Mide ve beyin dokularında HSP70 ile ER, ER, GPER ve glukortikoid reseptör ekspresyonları ölçüldü. Bulgular: Erkek, dişi ve OVX-sıçanlarda ER antagonistlerinin etkileri ve erkek ve dişilerde eksojen verilen ER agonistlerinin etkileri karşılaştırıldıktan sonra, OVX-dişi sıçanların bulguları E2’nin oksidan hasarı azaltıcı etkisinde üç ER’nin de rol alabildiğini ama ER’nin daha baskın rol aldığını gösterdi. Beyin, beyinsapı ve midede ER ekspresyonları dişi, erkek ve OVX-dişilerde ülsere bağlı farklı değişimler gösterdi. Sonuç: Bulgularımız, cinsiyetin, menopozun ve östrojen reseptörlerinin uyarılması veya inhibe olmasının stres ülserine yanıtı etkilediğini, östrojenin gastroprotektif etkisinin GPER, ERα ve ERβ reseptörlerinin ortak ve birbirine bağımlı aktivitesi ile gerçekleştiğini düşündürmektedir.
Objective: Stress-related mucosal injury is frequently seen in intensive care unit patients and its incidence is lower in premenopausal women than in men. In this thesis, it was aimed to elucidate the mechanisms of the protective effects of estrogen (E2) and estrogen receptors (ER) in the ulcer model (water restriction, WIRS) developed due to psychological stress in rats. Material and Methods: Male, female, or female rats that had undergone bilateral ovariectomy (OVX) 8 weeks ago were treated with WIRS for 6 hours, while rats in the control groups were only starved. E2, ER antagonists, ER agonists, or vehicle were administered subcutaneously for 3 days before applying the WIRS model. Blood flow, microscopic and macroscopic damage score, PGE2 level and oxidant stress parameters in the stomach; inflammatory cytokines, corticosterone and ACTH in serum were measured. Expressions of HSP70 and ER, ER, GPER and glucorticoid receptors were measured in stomach and brain tissues. Results: The effects of ER antagonists in male, female and OVX-rats and the effects of exogenously administered ER agonists in males and females were compared. Findings from OVX-female rats showed that all three ERs could play a role in the oxidant damage-reducing effect of E2, but ER played a more dominant role. ER expressions in the brain, brainstem, and stomach showed differential ulcer-related changes in females, males, and OVX-females. Conclusion: Our findings suggest that sex, menopause, and stimulation or inhibition of estrogen receptors affect the response to stress ulcer, and the gastroprotective effect of estrogen is mediated by the joint and interdependent activity of GPER, ERα and ERβ receptors.
Objective: Stress-related mucosal injury is frequently seen in intensive care unit patients and its incidence is lower in premenopausal women than in men. In this thesis, it was aimed to elucidate the mechanisms of the protective effects of estrogen (E2) and estrogen receptors (ER) in the ulcer model (water restriction, WIRS) developed due to psychological stress in rats. Material and Methods: Male, female, or female rats that had undergone bilateral ovariectomy (OVX) 8 weeks ago were treated with WIRS for 6 hours, while rats in the control groups were only starved. E2, ER antagonists, ER agonists, or vehicle were administered subcutaneously for 3 days before applying the WIRS model. Blood flow, microscopic and macroscopic damage score, PGE2 level and oxidant stress parameters in the stomach; inflammatory cytokines, corticosterone and ACTH in serum were measured. Expressions of HSP70 and ER, ER, GPER and glucorticoid receptors were measured in stomach and brain tissues. Results: The effects of ER antagonists in male, female and OVX-rats and the effects of exogenously administered ER agonists in males and females were compared. Findings from OVX-female rats showed that all three ERs could play a role in the oxidant damage-reducing effect of E2, but ER played a more dominant role. ER expressions in the brain, brainstem, and stomach showed differential ulcer-related changes in females, males, and OVX-females. Conclusion: Our findings suggest that sex, menopause, and stimulation or inhibition of estrogen receptors affect the response to stress ulcer, and the gastroprotective effect of estrogen is mediated by the joint and interdependent activity of GPER, ERα and ERβ receptors.