The Analysis of miRNA-mRNA Network Regulation Revealed the Mechanism of Different Drugs-Induced Constipation in Mice.

Abstract

Functional constipation (FC) is a common disease and high incidence in the digestive system. The pathogenesis of FC has not been thoroughly studied leading to a lack of effective therapeutic drugs. It is necessary to conduct in-depth research with animal experiments. The criteria for judging the success of the model and the method for evaluating the recovery of gastrointestinal function are the keys to animal experimental research on functional constipation. At present, the evaluation of the FC model is mainly based on the observation of defecation, as well as the detection of gastrointestinal transit and motility, which lack research at the genetic level. Therefore, this study chose antibiotic-, loperamide hydrochloride-, and sucralfate-induced FC mice model, and based on the observation of defecation reaction, the tissue changes of FC mice were observed by H&E staining and PAS staining, and then, the serum gastrin (GAS), acetylcholine (ACh), Motilin (MTL), substance P (SP), and vasoactive intestinal peptide (VIP) of FC mice were detected by ELISA. Finally, the effects of the three drugs on miRNAs in FC mice and the underlying mechanisms involved were analyzed by RNA-seq and bioinformatics. In conclusion, from analysis by RNA-seq and bioinformatics, miRNAs may be a factor leading to constipation, calcium-mediated signaling, cellular calcium ion homeostasis, endopeptidase activity, and G protein-coupled serotonin receptor activity were effector molecular function and biological process, and cell adhesion molecules (CAMs) was the effector signaling pathways.