| Part ? Establishment and evalution of a canine slow transit constipation modelAim:To establish a canine model of slow transit constipation(STC),then test the changes in gastrointestinal transit time,defecation and pathology.Methods:The gastrointestinal transit time(GITT),stool frequency and stool consistency were measured and recorded in 8 beagle dogs as baseline information.Then these dogs were randomly divided into the control group and the model group.Dogs in model group were given a diet of canned meat,as well as a combination of compound diphenoxylate and alosetron hydrochloride by oral for 5 weeks.Dogs in control group were given normal diet with no special intervention.GITT were measured every week,while stool frequency and stool consistency were observed and recorded daily.All animals went through the midline laparotomy and the colonic tissues were taken along the rectosigmoid colon,then investigated by light microscopy,electron microscopy,and immunohistochemistry to evaluate changes of protein gene product 9.5(PGP9.5),synaptophysin and c-kit between two groups.Results:It exhibited that GITT of the model group was prolonged(P=0.001).The stool became dry and hard in model group,with a reduced trend of both the stool frequency and stool consistency scores(P=0.043,P=0.002).After 5 weeks' intervention,in the model group,the myenteric neurons and interstitial cells of Cajal showed damage such as swelling of mitochondria under electron microscopy.Both of the PGP9.5 and synaptophysin integrated option density of rectosigmoid colon were decreased(P=0.013,P=0.046)in the model group under immunohistochemistry.The c-kit integrated option density showed no statistically significant difference between two groups.Conclusion:The canine model of STC consistent with clinical patients' symptoms and pathological changes was of successfully established,which can be used to observe and evaluate the therapeutic effect of colonic electric stimulation and so on.Part ? The effects of colonic electrical stimulation on gastrointestinal transit,defecation and enteric nervous system network in canine slow transit constipation modelsAim:To explore the effects of individualized colonic electrical stimulation on gastrointestinal transit and defecation in a canine slow transit constipation model.Then explore the influence on ENS-ICC-SMC network system.Methods:The gastrointestinal transit time(GITT),stool frequency and stool consistency were measured and recorded in 8 beagle dogs as baseline information.Then these dogs were randomly divided into colonic electrical stimulation group and sham stimulation group.All dogs underwent operation to implant the colonic electrical stimulation system.After a recovery period,a combination of a diet of canned meat,compound diphenoxylate and alosetron hydrochloride was given orally for consecutive 5 weeks.Colonic electrical stimulation(individual parameters selected before the first time of stimulation)/sham stimulation(simulated actions only,no electrical stimulation)were given from the second week.GITT were measured every week,stool frequency and stool consistency were observed and recorded daily.All animals went through the midline laparotomy and the colonic tissues were taken along the rectosigmoid colon,then investigated by light microscopy,and immunohistochemistry to evaluate changes of PGP 9.5,synaptophysin,c-kit in two groups.The differences of synaptophysin,c-kit,connexin43 and stem cell growth factor(SCF)evaluated under western blot.The histocompatibility of the implantable device was evaluated.Results:8 dogs went through all experiment items.Individual differences were found among the selected individualized parameters.Compared with the sham stimulation group,colonic electrical stimulation could shorten GITT(P=0.002),increase the frequency of defecation(P=0.042),and relieve the stool consistency score(P=0.035).Both of the PGP9.5 and synaptophysin integrated option density of rectosigmoid colon were increased(P=0.008,P=0.032)under immunohistochemistry,while the c-kit integrated option density showed no statistically significant difference between two groups.The expression of synaptophysin increased(P=0.002)under western blot,the expression of c-kit,connexin43 and SCF showed no statistically significant difference between two groups.No severe inflammation response was detected in the gross and microscopic appearance,and there was an ideal histocompatibility about the CES device.Conclusion:The individualized colonic electrical stimulation can relieve the constipation symptoms and promote the gastrointestinal transit in STC model dogs.The possible mechanism may be that the individualized colonic electrical stimulation induce regeneration of enteric nervous system myenteric plexus.There were ideal endurance and histocompatibility to the animals underwent colonic electrical stimulation. |
PDF Full Text Request