Clinical And Neuroimmunological Study On Early Oral Nutrition Improving Postoperative Ileus

Postoperative ileus(POI)often occurs in patients after major abdominal surgery,which might cause the increase of infectious complications and hospitalization cost and the extension of hospital stay.Currently,it is considered that the occurrence of postoperative ileus is a process of interaction between neuromodulation and inflammatory response.Early oral nutrition has been recommended as one of the measures to reduce postoperative ileus.More studies shown that early enteral nutrition(including early oral nutrition)can reduce inflammatory response which might improve postoperative ileus,while only a few studies focus on the effect of the feeding process and the nerve stimulation of the food itself on improving postoperative ileus and the designs of the research scheme were insufficient in these studies.It is very hard to judge the effect of early oral nutrition after improving neuromodulation on postoperative ileus.Meanwhile,mast cell-nerve axis is considered an important pathway for the interaction of neuromodulation and inflammatory response in postoperative ileus.It has been suggested that active transient receptor potential ankyrin-1(TRPA1)and cholecystokinin-1 receptor(CCK1-R)may be involved in the regulation of mast cell-nerve axis.However,it is not clear whether early oral nutrition plays a role in this pathway and whether TRPA1 and CCK1-R participate in the regulation of mast cell-nerve axis.In the first part of this study,a prospective,randomized controlled study was conducted to compare the incidence of postoperative ileus,the success rate of oral nutrition and the rate of infectious complications between the early oral nutrition group and the control group.The results showed that early oral nutrition regimen after increasing nerve stimulation improved postoperative ileus and oral nutritional success rate,which tended to shorten hospital stay.In order to further explain that early oral nutrition might improve postoperative ileus by mast cell-nerve axis,the second part of this study was was carried out on the mice model of postoperative ileus.After the establishment of the model,mices were randomly divided into TRPA1 inhibitor + eairly oral nutrition group,early oral nutrition group,postoperative ileus group and sham operation group.mRNAand protein expression of TRPA1 and CCK1-R from nerve cells,mast cell function and intestinal transport capacity.The results found that there were mast cell activation and degranulation during postoperative ileus.Early oral nutrition improved mast cell activation and degranulation.TRPA1 was involved in the occurrence of postoperative ileus.Eairly oral nutrition could increase the expression of mRNA and protein in TRPA1 in colon tissue and dorsal root ganglion and reduce the CCK1-R mRNA expression in intestinal smooth muscle;TRPA1 could reduce the activation of mast cells,TRPA inhibitor could increase the mRNA expression of CCK1-R and the concentration of portal vein blood;eai'ly oral nutrition could improve postoperative ileus by TRPA1 and CCKI-R participating in the regulation of mast cells-nerve axis.To further validate the crosstalk between mast cells and nerve cells at the cellular level and to explore the relationship between TRPA1 and CCK1-R in the crosstalk between mast cells and nerve cells,a mast cell-nerve cell non-contact coculture system was used for the first time,and then TRPA1,CCK1-R and mast cells were given to the corresponding cells in the co-culture system.The results shown that TRPA1 and CCK1-R were involved in the crosstalk between nerve cells and mast cells.TRPA1 regulated the function of mast cells by modilating CCK1-R,which is one of the mechanisms of TRPAI regulating of mast cells.