Evaluation of endoplasmic reticulum stress and relative changes in jejenum and terminal ileum adaptation in the rat model of short bowel syndrome

Aim: There are a lot of studies on endoplasmic reticulum stress (ERS) which has been associated with various diseases. However, in the intestinal adaptation induced by massive small bowel resection (MSBR), the role of ERS has not been investigated in the literature. In this study, it was aimed to determine the relationship between ERS and the adaptation process in the jejunum and ileum of rats undergoing MSBR using immunohistochemical method. Material and Method: In this study, a total of 70 Wistar rats, aged 8-10 weeks, were divided into 3 main groups: Control (C) group (n=10), Sham (S) group (n=30) and Resection (R) group (n=30) S and R groups were divided into subgroups with 10 rats each according to the phases of adaptation proess to be sacrificed at the end of the phases (acute phase: 0-3 days, early adaptive phase: 4-9 days, maintenance phase: 10-15 days). No surgical procedure was performed in the C group. In group S, the terminal ileum was transected and anastomosis was performed. In the R group, 75% MSBR was performed and SBS model was achieved. After surgery, the animals were monitored daily for weight changes. At the end of the follow-up period, macroscopic/morphological measurements of the small and large intestines of the sacrificed animals were taken. Jejunum and ileum tissues were evaluated by light microscopy in terms of villus lengths, crypt depths and muscle thicknesses. The expressions of GRP78 as an ERS marker, and CHOP as a pro-apoptotic ERS marker were immunohistochemically evaluated. Result: The mortality of the study was 8.3% and the experiment was completed with 65 animals. A significant weight loss was observed in the R group. In group S, histopathological changes in the ileum showed complex features. In the R group, elongation of villi, increase in crypt depth and muscle thickness in the jejunum and ileum were observed starting from the acute phase of adaptation compared to the C and S groups. In the jejenum tissues of R groups GRP78 expression was significantly higher in all adaptation phases compared to the S and K groups. In the S groups, GRP78 expression was increased compared to the C group on days 3 and 9 while it was significantly weaker than in the R group on day 9. In the ileum of R group, GRP78 expression showed no significant difference compared to the S group but showed a significant increase on the 9th day compared to the C group. In the jejenum tissues of the R groups, CHOP expressions did not differ significantly compared to the C group but in the S groups showed significant increase compared to the C and R groups on days 3 and 9. The CHOP expressions in the ileal tissues of R groups showed significant suppression on day 3, while on day 9 the S and R groups showed a significantly increased expression compared to the C group . Conclusion: Our morphometric and histopathological data support that our experimental model based on MSBR constitutes SBS. While GRP78 had a more homogeneous interaction with the adaptation process, especially in the jejunum, CHOP showed a heterogeneous interaction with the adaptation process in the ileum. Additionally, it was observed that there were findings related to both GRP78 and CHOP during the adaptation process of S groups. Therefore, the interaction of ERS with the adaptation process in the jejunum and ileum has quite complex features. Therefore, there is a need for studies that will examine in more detail the role of ERS in the adaptation process of the small intestines in CBS. Key Words: short bowel syndrome, massive small bowel resection, endoplasmic reticulum stress, GRP78, CHOP