Mechanism Of Teduglutide Combined With Dietary Fiber In Promoting Intestinal Adaptation

Background and purpose:It is a clinical consensus that Enteral nutrition is able to help improve bowel function after surgery. In recent years, some studies showed that to give exogenous glucagon like peptide-2(GLP-2) can promote intestinal adaptation response after extensive small bowel resection. The compensatory changes of the entire intestinal tract and body on the levels of cells, tissues, organs and systems after extensive small bowel resection is called intestinal adaptation. The specific performance includes the enlargement of the intestinal lumen, the hypertrophy of mucosal (especially the ileum), the growth of villus, the increase of absorption cells and the increase of effective absorption area in unit length. In this study, the short bowel model of rats was established, to investigate the effect of (GLP-2) and dietary fiber, alone or in combination, on the adaptability of the left small intestine.Method:85%of the small intestine was removed by microsurgical techniques to form a short bowel model. Rats were divided into short bowel control (EN) group, teduglutide group (EG), dietary fiber (EF) group and teduglutide&dietary fiber (EGF) group according to the given nutrition postoperatively. Rats’state were observed after the surgery.10days after surgery the intestine and colon specimens were taken and observed with HE staining of the histological changes (mainly referring to the villus height and crypt depth). Intestinal epithelial PCNA and caspase-3expression were detected by immunohistochemical staining to determain the of epithelial proliferation and apoptosis level. The mRNA expression of small intestine Pept-1, SGLT-1were detected by RT-PCR.ResuIts:Pairwise comparisons of rats’ jejunum&ilieum villus height:There is significant difference when comparing EGF group to EF group, EN group respectively(P<0.01), EG group to EN group; no significant difference (P>0.05) of EG group to EGF group. DG group compared to EF group showed significant difference on ilieum villus height(P<0.05) but no significant difference on jejunum villus height(P>0.05).Pairwise comparison of the rats’ colon mucosa thickness and intestinal wall thickness:There is significant difference when comparing EGF group to EN, EG group respectively(P<0.01). but no significant difference when compared to EF group(P>0.05). EG group and EN group had no significant difference comparely(P>0.05). The comparation between EF and EN group had significant difference on both mucosa thickness(P<0.01) and intestinal wall thickness(P<0.05). And between EF and EG group there was significant difference on mucosa wall thickness(P<0.05) but no significant difference (P>0.05) on intestinal wall thickness.Rats’ jejunum and ileum intestinal epithelial proliferation and apoptosis:There is significant difference when comparing EGF group to EF, EN group respectively(P <0.01), and EG group to EF group(P<0.05), EN group respectively(P<0.01); no significant difference (P>0.05) of EGF group to EG group, and EF group to EN group.the total RNA of ilieum mucosa unit was amplified by RT-PCR, where the volume of β-actin varied slightly between each animal. The ilieum Pept-1and Sglt-1expression of EGF group was significantly higher than EF group and EN group (P <0.01); while there is also significant difference when EG group compared with EF group(P<0.05) and EN group (P<0.01), same as EF group with EN group(P<0.05); no significant difference between EG group and EGF group on either Pepet-1or Sglt-1expression.Conclusion:1. Dietary fiber can significantly promote the growth of mucosa and the intestinal wall, and improve the recovery of the structure of the small intestine mucosa.2. The exogenous administration of teduglutide(GLP-2) could promote intestinal cell proliferation, increase intestinal absorption area, reduce epithelial apoptosis, thereby improve bowel function. 3. The application of teduglutide and dietary fiber alone or in combination can promote the remnant small intestine compensatory hyperplasia in rats after extensive small bowel resection. Moreover, teduglutide and dietary fiber performe synergy to strengthen the entire intestine adaptation.