Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury  

作　　者：Bo Cao Rui-Yang Zhao Hang-Hang Li Xing-Ming Xu Hao Cui Huan Deng Lin Chen Bo Wei 

机构地区：[1]Department of General Surgery,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China [2]Medical School of Chinese PLA,Beijing 100853,China

出　　处：《Military Medical Research》2023年第1期78-93,共16页军事医学研究（英文版）

基　　金：funded by the National Basic Research Program of China(2019YFB1311505);the National Natural Science Foundation of China(82073192,81773135)。

摘　　要：Background: Traumatic colon injury(TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However, there is a lack of basic research in this field.This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield.Methods: A total of 669 Sprague–Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay(ELISA) was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase, D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis, the relative abundances of specific bacterial genera were detected using quantitative real-time PCR(qRT-PCR).Results: As a type of lethal injury, TCI induced acute disruption of intestinal homeostasis, characterized by inflammatory responses, intestinal barrier hyperpermeability and microbiota dysbiosis(P<0.05). Significant alterations in bacterial metabolic patterns were detected with decreases in many metabolites. After a series of screenings,we found that oral administration of asparagine(Asn) and 3-indolepropionic acid(IPA) effectively prolonged posttraumatic survival time [Asn plus IPA vs. Vehicle: hazard ratio(HR)=0.105, 95%CI 0.031–0.356, P=0.0003] and restored intestinal homeostasis in TCI rats(P<0.05). Mechanistically, this combinational strategy protected the rats against TCI through

关 键 词：Traumatic colon injury ASPARAGINE 3-Indolepropionic acid Intestinal homeostasis Intestinal microbiota Akt signaling 

分 类 号：R82[医药卫生—临床医学] R-332