Alteration of Cajal Cells in Colonic Tissue of Slow-transit Motility Model in Mouse

Background:The pathogenesis of slow transit constipation is unknown in most cases.The interstitial cells of Cajal(ICCs)have been increasingly recognized as the cells acting as gastrointestinal pacemaker and neurotransmitter mediator.Furthermore,the abnormal changes of the number and structure of ICC have been described in a variety of gastrointestinal motility disorders.Aims:To appraise the changes of ICCs in colonic tissue of slow-transit colonic motility mouse model.Methods:The mouse model was constructed by subcutaneous injection of morphine.Proximal and distal colonic tissues were obtained and the expression and distribution of ICCs were observed by immunohistochemistry.c-Kit protein and c-kit mRNA were detected by Western blot and reverse transcriptase polymerase chain reaction(RT-PCR),respectively.Results:①In the proximal colonic tissues,the surface area of c-kit positive cells in the test groups decreased significantly compared with that in the control group(P0.01),and that in the test group Ⅱ was less than that in the test group Ⅰ after 45 days(P0.01).The surface area of c-kit positive cells in the group after stopping of morphine was less than that in the groups given naloxone and in the control group after 60 days(P0.01).There were no differences between all test groups and the control group in the surface area of c-kit positive cells of distal colonic tissue.②In the proximal colonic tissue,the c-Kit protein and c-kit mRNA in the test groups decreased significantly when compared with the control group after 45 days(P all 0.01).The levels of c-Kit protein and the expression of c-kit mRNA in the group after stopping of morphine were lower than those in the groups given naloxone and in the control group,respectively after 60 days(P0.05 and P0.01).Conclusions:The amount of c-kit positive cells,c-Kit protein and c-kit mRNA decreased obviously in the proximal colonic tissue of morphine-induced slow-transit colonic motility.These suggest that the changes of ICCs might be one of the factors involved in the slow-transit colonic motility,which could not be reversed after stopping of morphine.However,by given naloxone,the amount of ICCs fundamentally recovered with improvement of colonic motility,this suggests that naloxone can block and promote the recovery of morphine-induced ICC alteration.