The Effects And Mechanism Of Interstitial Cells Of Cajal In Visceral Hyperalgesia In Rats With Irritable Bowel Syndrome

Objective:Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinaldisorders in the world, which affected the quality of people’s lives, but we have no strategyto treat it, its pathogenesis is still unclear, its remarkable characteristic is the existence ofvisceral hyperalgesia, which is characterized by chronic abdominal discomfort, pain andbloating, changed habits of defecation. Visceral hyperalgesia is closely linked with thebrain-gut axis have been confirmed.Recently, the IBS patients have been especially foundthe mast cell is significantly activated, which made the low-grade inflammation andimmunological alterations in the gut, that play a very important role in the pathogenesis ofvisceral hyperalgesia of IBS. Research show that the interstitial cells of Cajal (ICC), itsspecific receptor c-kit, which can bind to ligand stem cell factor (SCF), combine to form two dimmer of SCF/c-kit,which can secrete bioactive substances and activate the mastcells. Therefore, the gastrointestinal tract of interstitial cells of Cajal will play a veryimportant role in visceral hyperalgesia, in this experiment research on the interstitial cellsof Cajal in the mechanism of visceral hyperalgesia of IBS. Open up a new path for themechanism of visceral hyperalgesia of IBS.Methods:①Using the trichinella apiralis made the model rats of IBS.②With intraperitonealinjection of STI-571to the model rats of IBS, made the IBS rats of blocking SCF/c-kit.③With fluorocitrate enema model rats of IBS, made the IBS rats of blocking gastrointestinalglial cells.④Application of electrophysiological method to observe the myoelectricchanges of rectus abdominis and record the change of discharge frequency of DCN, usethe immunofluorescence method to observe the expression of the ICC in colon, the Cx43in colon and NMDAR2in DCN.Results:1. IBS rats after the stimulation of colorectal distention, the expression of ICC, themyoelectric changes of rectus abdominis and the DCN discharge frequency weresignificantly increased than in the normal control group, normal colon group, IBS groupand IBS colon STI-571expansion stimulation group (P<0.01), and the normal group, thenormal with the stimulation of colorectal distention, IBS group and STI-571to the IBSwith the stimulation of colorectal distention had no obvious difference (P>0.01).2. IBS rats after the stimulation of colorectal distention, theirs Cx43and NMDAR2were significantly increased than the normal control group, normal group with thestimulation of colorectal distention, IBS group and STI-571to the IBS rats with thestimulation of colorectal distention (P<0.01). The normal rats, the normal rats with thestimulation of colorectal distention, IBS rats and STI-571to the IBS rats with thestimulation of colorectal distention had no obvious difference (P>0.01). 3. With fluorocitrate to the IBS rats of the stimulation of colorectal distention, themyoelectric changes of rectus abdominis,the expression of NMDAR2and the dischargefrequency of DCN were no significantly differences than IBS after the stimulation ofcolorectal distention and IBS rats(P>0.01). With fluorocitrate to the IBS rats of thestimulation of colorectal distention, the myoelectric changes of rectus abdominis,theexpression of NMDAR2and DCN discharge frequency were significantly increased thanthe normal control group, normal group with the stimulation of colorectal distention andIBS rats(P<0.01).Conclusion1. SCF/c-Kit regulated activation of interstitial cells of Cajal plays a very importantrole in visceral hypersensitivity of IBS, the blocking of SCF/c-kit significantly reduced thevisceral hyperalgesia of IBS.2. High expression of Cx43of colon in IBS rats with the stimulation of colorectaldistention, suggesting that they are closely linked with visceral hyperalgesia of IBS,blocking the SCF/c-kit of interstitial cells of Cajal, reduce the expression of NMDAR2,suggesting that ICC may affect the central administration to impact on visceralhyperalgesia of IBS.3. After the specific inhibition fluorocitrate blocking the gastrointestinal microglial,whereas the visceral hyperalgesia of IBS rats did not decrease, prompting that in thegastrointestinal tract, ICC may play a major role in the visceral hyperalgesia of IBS.