| AIMS: Chronic inflammatory processes and gastric contents related esophageal mucosalinjury are two major characteristics of reflux-related erosive esophagitis (RE). This study wasaimed to establish a chronic acid reflux esophagitis rat model fitting RE major characteristicsthrough surgically induced incomplete pyloric obstruction, with minimized surgical damage.Moreover, the effect of mosapride, one of the5-hydroxytryptamine4(5-HT4) receptoragonists, on the reflux-related inflammation of esophageal mucosa of rats were explored.Method:1. Pyloric clips were made by flat PVC twist ties. SD rats were divided into fourgroups randomly, including3.9mm group,4.2mm group and4.5mm group (according to theinner diameter of pyloric clip,15rats respectively), and sham-operation control group (10rats). Conventional animal celiotomy were performed, and the pyloric clips were placed crossthe rats’ gastroduodenal junction. The pyloric clip was closed by surgical suture3-0, while theother end of suture was used for the ligation of2/3part of the gastric fundus. Rats weresacrificed2weeks later and the esophageal tissues were taken for histological examination.2.According to mosapride dosages administrated, Pyloric Clip-induced Chronic Acid RefluxEsophagitis (PC-CARE) rats were randomly divided into four groups, including0.1mg/kg,0.5mg/kg and2.5mg/kg groups and saline control group (3rats, respectively). After24hstarve,3.5mL of rice soup was gavaged into the stomach in each group. Rats were sacrificed2h later. After pyloric and cardia ligation, the weight of stomachs and contents were recorded.According to mosapride dosages administrated, PC-CARE rats were randomly divided into0mg/kg/d (as blank control),0.1mg/kg/d,0.5mg/kg/d and2.5mg/kg/d groups (15ratsrespectively). A sham-operation control group (10rats) was set. Rats were gavaged by0.5%CMC diluted mosapride (treatment groups) or0.5%CMC in the same volume only (blankcontrol and sham-operation groups). Rats were sacrificed2weeks later, the esophageal tissues were prepared for histological examination and immunohistochemistrical detection (ABCmethod) of ED-1(a lysosomal monocyte/macrophage antigen) expression.45Rats withPC-CARE were orally gavaged with0.5mg/kg/d mosapride. According to the drugs anddosages administrated via tail vein injection, the rats were randomly divided into three groups,including1.0mg/kg/d of5-HT4receptor antagonist GR113808group (G group),0.3mg/kg/dof acetylcholine (Ach) receptor antagonist methyllycaconitine group (M group) and0.1mL/100g saline group (C group, as control)(15rats, respectively). Rats were sacrificed2weeks later and the esophageal tissues were taken for histological examination.Result:1. The2-week survival rates of the3.9mm group,4.2mm group,4.5mm group andsham-operation control group were26.7%,73.3%,86.7%and100%, respectively, while theincidences of RE were75.0%%,72.7%,15.4%and0, respectively. No significant differencewas found between4.5mm and4.2mm groups in the survival rates (P>0.05), while theincidences of RE showed significant difference between4.5mm and4.2mm groups(P<0.05).2. No significant difference was found in the residual rate of rice soup in stomachPC-CARE rats treated with different dosages of mosapride.3.The esophagitis grades in0.5mg/kg/d and2.5mg/kg/d mosapride groups were lower than that in blank control group(P<0.05), while no significant difference was found between those two mosapride treatedgroups (P>0.05).4.The counts of ED-1positive cells in esophageal tissues were foundsignificantly higher in mosapride treated rats than that in blank control group (P<0.05).5.Theesophagitis grades in G and M groups were higher than that in C group (P<0.05), while nosignificant difference was found in that between G and M groups (P>0.05).Conclusion: A chronic acid reflux esophagitis rat model was established by pyloric clipinduced incomplete pyloric obstruction and part of the gastric fundus ligation. The model hasa high long-term survival rate and a high incidence of RE, while the surgical damage wasminimized. Mosapride may have anti-inflammatory effect on RE, which is related with5-HT4receptor and Ach nerve system activation, but not its prokinetic effects. |
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