Lili ZHANG, Xiang 1 ZHONG, Tian 1 WANG, Jintian 1 HE, Daryoush BABAZADEH, Ligen 1 ZHANG, Farman Ali 1 SIYAL, Chao WANG

Kolostruma Cevap Veren Rat Yavrularında İntrauterin Büyüme Geriliği İntestinal Otofaji ve Proliferayonu Artırır

Bu çalışmanın amacı, rat modeli üzerinde otofaji, apoptozis ve proliferasyonu incelemek suretiyle intrauterin büyümesi kısıtlanan (IUGR) yavrularda hızlı intestinal büyümeden sorumlu mekanizmaları araştırmaktır. Yirmi adet bir doğum yapmış anneler iki gruba ayrıldı; 1) ad libitum beslenen (Adlib) anneler ve 2) Gestasyonun 10 ile 21. günü arasında yemi %50 kısıtlanan anneler. Böylece normal doğum ağırlığı (NBW) olan yavrular ve IUGR yavrular elde edildi. Doğumda yavru sayısı ve ağırlıkları kaydedildi ve her batında 8 yavru 24 saat süresince yeterli kolostrum alması için annesi ile birlikte tutuldu. Sonrasında, her batından 2 yavruya dekapitasyon uygulandı. Elde edilen sonuçlar yemi kısıtlanan annelerin yavru sayıları ile Adlib grubun yavru sayılarının benzer olduğunu ancak IUGR yavrular ürettiğini gösterdi. Histolojik incelemede IUGR ratların jejunumda azalmış villus yüksekliğine ve yüzey alanına sahip olduğu belirlendi. IUGR yavruların jejunum mukozasında otofagozomların oluştuğu ancak mitokondri ve mikrovillusların etkilenmediği gözlemlendi. IUGR yavruların jejunumlarında WIPI1, MAP1LC3B, Atg13, ULK1 ve Beclin1 mRNA ekspresyonlarının arttığı ve mTOR ekspresyonunun azaldığı belirlendi. Bu hayvanlarda daha düşük Bcl-2 mRNA ekspresyonu, artmış caspase 9 ve orantısal olarak artmış ki67 mRNA ekspresyonu tespit edildi. Elde edilen sonuçlar kolostrum ile besleme sonrası IUGR yavrularda histolojik olarak mitokondrilerde bir değişim olmaksızın jejunumda hasarın oluştuğunu gösterdi. Düşük stres altında gelişmiş intestinal otofaji, intestinal proliferasyonu iyileştirebilir ve bu durum hızlı intestinal büyümeye katkı sağlayabilir

Intrauterine Growth Retardation Enhances Intestinal Autophagy and Proliferation in Rat Pups Responding to Colostrum

This study aimed to investigate responsible mechanisms for rapid intestinal catch-up growth in intrauterine growth restriction (IUGR) pups via analysis of autophagy, apoptosis and proliferation in a rat model. Twenty primiparous dams were assigned into two groups as 1) dams with feed ad libitum (Adlib) and 2) dams with 50% feed restriction from gestational day 10 to 21 to achieve normal birth weight (NBW) and IUGR pups, respectively. Litter size and pup weight were recorded at parturition and 8 pups were kept in each litter to have sufficient colostrum for 24 h. Subsequently, 2 pups from each litter were decapitated. Results indicated that feed restriction dams had similar litter size with rats in Adlib group although produced IUGR pups. Histological analysis indicated that IUGR rats had decreased villus height and surface area in jejunum. There was an accumulation of autophagosomes in jejunal mucosa of IUGR pups, however, the mitochondria and microvilli were unaffected. mRNA expressions of WIPI1, MAP1LC3B, Atg13, ULK1 and Beclin1 were increased, and mTOR expression was decreased in jejunum of IUGR, which also had lower Bcl-2 mRNA expression, increased caspase 9 and relative increased ki67 mRNA expression. Results suggested that after feeding colostrum, IUGR pups had impaired jejunum with unaffected mitochondrial histology. Enhanced intestinal autophagy under low-stress conditions might improve intestinal proliferation, which may be contributed to the rapid intestinal catch-up growth.

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