Effect Of Nimesulide On Chemoprevention Of Chronic Atrophic Gastritis And Expression Of P 16 In Stomach Mucous Membrane

Objective: This study was designed to construct the rat model with chronic atrophic gastritis (CAG), and observe the preventive effect of cyclooxygenase (COX)-2 inhibitor nimesulide on CAG rats, then try to investigate the molecular mechanism to provide theoretical evidence for the chemical prophylaxis of chronic atrophic gastritis .Methods: 72 male rats (6-week) were divided into 6 groups, each group drinked different drugs: control group (normal); CAG model; nimesulide group with different dose (4mg, 6mg, 8mg per rat); positive group (folacin). Rats' consciousness, appetite, glossiness of clothing hair, sedes and body weight were observed. All the rats were killed after 24 weeks' breed, their stomach mucous membrane were viewed by HE staining; The expression of COX-1, COX-2 and P16 protein in mucous membrane epithelioid cells were detected by immunohistochemistry. Data from each experiments were expressed as mean±SD. Measurement data were analyzed by F test and enumeration data were byχ2 test by using SPSS 13.0 software, P<0.05was considered significant.Results: There were 66 rats remaining after 24 weeks' feeding. The CAG incidence rate was significant difference than control in model group (P<0.01), indicated that the model was established successfully. The body weight of model rat was lower than normal group, nimesulide and folacin group (P<0.01), there is no significant difference between other groups (P<0.05). As for the precaution, nimesulide group and positive group could prevent CAG (P<0.05), but there was no significant difference between different dose of nimesulide group and positive group (P>0.05). COX-1 were expressed in each groups, and there was no difference between them. The expression level of COX-2 and p16 protein were different between model and nimesulide groups (P<0.05), but there is no statistical significance between nimesulide and falacin group.Conclusion1. Nimesulide could prevente the occurrence of N-ethyl-N-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis in rat;2. Nimesulide could up-regulate the expression of P 16 in stomach mucous membrane of N-ethyl-N-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis in rat.