Deneysel intrauterin yapışıklık modeli oluşturulan sıçanların uterusunda ghrelin etkilerinin incelenmesi
Küçük Resim Yok
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
İntrauterin adezyon östrus siklusta düzensizlik, akut alt karın ağrısı, tekrarlayan gebelik kayıpları ve infertilite gibi etkileri olan bir hastalıktır. İntrauterin adezyonların rutin bir tedavi protokolü ve nüksünün önlenmesinde standart bir uygulama mevcut değildir. Ghrelin, midede endokrin X (A) hücreleri tarafından salgılanan 28 aminoasitlik peptit bir hormondur. Ghrelin, pek çok nörolojik ve fizyolojik süreçte rol üstlenmektedir. Bu rollerine ek olarak, çeşitli organ sistemlerinde immünmodülatör, antiinflamatuvar, antifibrotik ve antioksidan etkiler gösterdiği bilinmektedir. Deneysel intrauterin adezyon modeli oluşturulan sıçanlarda ghrelin etkinliğinin histolojik olarak değerlendirilmesi temel amaçtır. Çalışmada; kontrol, intrauterin adezyon modeli, düşük doz ghrelin ve yüksek doz ghrelin uygulaması yapılan, toplam dört gruba ayrılan 28 adet dişi sıçan kullanılmıştır. Menstrüal siklusları eşitlenen sıçanlarda deney modeli oluşturmak için sağ uterus boynuza 20 G branül ile transvajinal 0,2 ml trikloroasetik asit enjeksiyonu yapılmıştır. Üç östrus siklus sonra sıçanlara 20 ng/kg ve 40 ng/kg dozunda ghrelin i.p. olarak 7 gün boyunca enjekte edilmiştir. Deney sonunda anestezi altında sakrifiye edilen dişi sıçanların uterus dokuları rutin histolojik takibe alınmıştır. Uterus dokularının histokimyasal incelemeleri için; Hematoksilen-Eosin ve Masson trikrom boyamaları, immünohistokimyasal incelemeler için; anti-VEGF, anti-kolajen 1, anti-TNF?, anti- FGF2 ve anti-HIF-1? belirteçleri kullanılmıştır. Sıçanlarda ghrelin uygulaması sonrası kilo alımı incelendiğinde 5. gün ve sonrasında günler arası tüm ikili farkların anlamlı olduğu ve deneklerde ağırlık artışı olduğu belirlendi (p<0,001). Uterus duvar kalınlığı ve endometriyum kalınlık ölçümleri yapıldı. Adezyon grubunda duvar kalınlığının en düşük olduğu saptandı ve ghrelin uygulamasının endometriyum kalınlığını arttırdığı saptandı (p<0,001). Histopatolojik olarak adezyon grubunda epitel değişikliği, lümende daralma, endometriyal bağ dokusunda inflamasyon ve fibrozis, uterinal bezlerde de dejenerasyon saptandı. Ghrelin tedavisinin bu bulguları geriye çevirdiği saptandı. İmmünohistokimyasal boyama sonuçlarında ise adezyon gruplarında tip 1 kolajen, TNF?, HIF-1? ve FGF2 ekspresyonunun deney grupları arasında en yüksek seviyede olduğu görüldü. Ghrelin gruplarında doz bağımlı olarak bu ekspresyonların azaldığı saptandı. VEGF ekspresyonu ise adezyon grubunda en düşük seviyede olduğu görülürken, ghrelin gruplarında doz bağımlı olarak ekspresyonun arttığı saptandı. Sonuç olarak ghrelinin intrauterin adezyonların tedavisinde olumlu etkiler gösterdiği görülmüştür. Bu konuda yapılacak ileri deneysel ve klinik çalışmalar ghrelinin intrauterin adezyon tedavisinde kullanımı ile ilgili yeni gelişmelere ışık tutacaktır
Intrauterine adhesion is a disease with effects such as irregularity in the estrous cycle, acute lower abdominal pain, recurrent pregnancy loss and infertility. There is no routine treatment protocol for intrauterine adhesions and no standard practice for the prevention of recurrence. Ghrelin that has a role in various neurological and physiological processes, controls hunger and metabolic regulation, is a 28 amino acid peptide hormone secreted by endocrine X (A) cells in the stomach. Ghrelin plays a role in many neurological and physiological processes. In addition to these roles, it is known to have immunomodulatory, anti-inflammatory, antifibrotic and antioxidant effects in various organ systems. Histological evaluation of ghrelin activity in rats with experimental intrauterine adhesion model is the main aim of the present study. In the study; A total of 28 female rats, which were divided into four groups, were used as control, intrauterine adhesion model, low-dose ghrelin and high-dose ghrelin administration. To create an experimental model in rats whose menstrual cycles were equalized, 20 G branula and 0.2 ml of trichloroacetic acid were injected transvaginally into the right uterine horn. After three oestrus cycles, ghrelin was administered i.p. to rats at 20 ng/kg and 40 ng/kg, and injected for 7 days. At the end of the experiment, the uterine tissues of female rats sacrificed under anesthesia were routinely followed histologically. . For histochemical examinations of uterine tissues, Hematoxylin and Eosin and Masson trichrome stainings were performed, while Anti-VEGF, anti- collagen 1, anti-TNF?, anti-FGF2 and anti-HIF-1? markers were used for immunohistochemical examinations. When weight gain after ghrelin administration in rats was examined, it was determined that all bilateral differences between days were significant and weight gain was observed in the 5th day and later (p<0.001). As a result of the measurement of wall and endometrium thicknesses, it was determined that the wall thickness was the lowest in the adhesion group, and it was determined that ghrelin application increased the endometrial thickness (p<0.001). Histopathologically, epithelial changes, narrowing of the lumen, inflammation and fibrosis in the endometrial connective tissue, and degeneration in the uterine glands were detected in the adhesion group. It was found that ghrelin treatment reversed these findings. In the immunohistochemical staining results, it was observed that the expression of type 1 collagen, TNF?, HIF-1? and FGF2 in the adhesion groups was the highest among the experimental groups. It was determined that these expressions were decreased in a dose-dependent manner in the ghrelin groups. While VEGF expression was observed to be at the lowest level in the adhesion group, it was determined that the expression increased in a dose-dependent manner in the ghrelin groups. As a result, it has been observed that ghrelin has positive effects in the treatment of intrauterine adhesions. Further experimental and clinical studies on this subject will shed light on new developments regarding the use of ghrelin in the treatment of intrauterine adhesions.
Intrauterine adhesion is a disease with effects such as irregularity in the estrous cycle, acute lower abdominal pain, recurrent pregnancy loss and infertility. There is no routine treatment protocol for intrauterine adhesions and no standard practice for the prevention of recurrence. Ghrelin that has a role in various neurological and physiological processes, controls hunger and metabolic regulation, is a 28 amino acid peptide hormone secreted by endocrine X (A) cells in the stomach. Ghrelin plays a role in many neurological and physiological processes. In addition to these roles, it is known to have immunomodulatory, anti-inflammatory, antifibrotic and antioxidant effects in various organ systems. Histological evaluation of ghrelin activity in rats with experimental intrauterine adhesion model is the main aim of the present study. In the study; A total of 28 female rats, which were divided into four groups, were used as control, intrauterine adhesion model, low-dose ghrelin and high-dose ghrelin administration. To create an experimental model in rats whose menstrual cycles were equalized, 20 G branula and 0.2 ml of trichloroacetic acid were injected transvaginally into the right uterine horn. After three oestrus cycles, ghrelin was administered i.p. to rats at 20 ng/kg and 40 ng/kg, and injected for 7 days. At the end of the experiment, the uterine tissues of female rats sacrificed under anesthesia were routinely followed histologically. . For histochemical examinations of uterine tissues, Hematoxylin and Eosin and Masson trichrome stainings were performed, while Anti-VEGF, anti- collagen 1, anti-TNF?, anti-FGF2 and anti-HIF-1? markers were used for immunohistochemical examinations. When weight gain after ghrelin administration in rats was examined, it was determined that all bilateral differences between days were significant and weight gain was observed in the 5th day and later (p<0.001). As a result of the measurement of wall and endometrium thicknesses, it was determined that the wall thickness was the lowest in the adhesion group, and it was determined that ghrelin application increased the endometrial thickness (p<0.001). Histopathologically, epithelial changes, narrowing of the lumen, inflammation and fibrosis in the endometrial connective tissue, and degeneration in the uterine glands were detected in the adhesion group. It was found that ghrelin treatment reversed these findings. In the immunohistochemical staining results, it was observed that the expression of type 1 collagen, TNF?, HIF-1? and FGF2 in the adhesion groups was the highest among the experimental groups. It was determined that these expressions were decreased in a dose-dependent manner in the ghrelin groups. While VEGF expression was observed to be at the lowest level in the adhesion group, it was determined that the expression increased in a dose-dependent manner in the ghrelin groups. As a result, it has been observed that ghrelin has positive effects in the treatment of intrauterine adhesions. Further experimental and clinical studies on this subject will shed light on new developments regarding the use of ghrelin in the treatment of intrauterine adhesions.
Açıklama
03.07.2023 tarihine kadar kullanımı yazar tarafından kısıtlanmıştır
Anahtar Kelimeler
Histoloji ve Embriyoloji, Histology and Embryology