Comparison of the Different Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Mice in the Enteric Nervous System

Abstract Background As “the second brain”, the gastrointestinal tract contains an intrinsic neuronal network: the Enteric Nervous System (ENS). The ENS governs motility, fluid homeostasis, and blood flow, and it also works with other parts of the intestine, playing a vital role in the occurrence and development of IBS-D. Methods To assess the effects of different IBS-D rat models (life stress, chemical enema stimulation, and compound stimulation ) on the ENS, we have established three models of BALB/c mice by wrapping restrain stress (WRS), a single administration of trinitro-benzene-sulfonic acid with 50ul (TNBS, 2mg/mouse in 50% ethanol), and WRS + TNBS. We have also determined Cytokine levels, the activity of intestinal neurons, intestinal mucosal barrier function, intestinal neurotransmitters, and structural changes of intestinal nerve cells after inducing IBS-D. Results This research found that the intervention of TNBS + WRS, WRS, and TNBS would induce a similar course of effects on the ENS. Among the three models, the distance at the open-field test decreased with speed, AWR scores (at 0.6ml), and intestinal permeability all increased. The levels of 5- hydroxytryptamine in colon tissue rapidly increased, whereas serum showed no significant changes. Using TEM to observe monocyte cells infiltrating neuronal cells and the structural changes in neurons. According to Western blot, HTR3A, C-fos level increased, and PGP9.5 decreased in TNBS + WRS and WRS modeling groups. Using the LEGENDplex™ detection kit to assess 13 mouse cytokines for colon tissues, we found that some inflammation factors significantly changed in the TNBS + WRS group. Conclusion This study depicts a general description of the major processes through which the tumor itself causes fatigue and renders a standard and reliable animal model for further pharmacological or pharmacodynamic studies.