| Objective Gastric cancer is the most common gastrointestinal cancer, the incidence and mortality rates rank in our country are the top level. Omeprazole(omeprazole, OME) is an very important drug for the treatment of digestive diseases, such as peptic ulcer disease. Whether long-term OME administration in patients will increase the incidence of gastric cancer or promote the development of gastric cancer. This study was designed by the mice drinking water containing methyl nitro- nitrosoguanidine(N-methyl-N’-nitro-N-nitrosoguanidine, MNNG) drinking water induced mouse model of gastric cancer, to investigate long-term OME administration will increase the incidence of gastric cancer in mice and analysis the possible mechanism.Methods Males Ku-Ming mice(weight range 18–220g) were randomly divided into six groups: simple control group(control, CON, n = 7), low dose OME group(n = 7), high dose OME group(n = 7), MNNG group(n = 14), MNNG + low-dose OME group(n = 14), MNNG + high-dose OME group(n = 14). MNNG group, MNNG + low dose OME group and MNNG + high dose OME group, three groups of mice is added MNNG 100 mg / L in drinking water. Low-dose OME group, MNNG + low-dose OME group, high-dose OME group and MNNG + high-dose OME group, were start given a gavage of OME, low dose group at a dose of 6 mg/kg, high-dose group at a dose of 30 mg/kg, once a day for 24 wk. MNNG group and simple control group were given an equal volume of normal saline(NS). Weighing mouse body weight once a week. After the start of the experiment 14 wk, MNNG group, MNNG + low dose OME group and MNNG + high dose OME group were randomly selected five mice sacrificed. HE staining was used to detect the pathology changes of stomach. After 24 wk mice were sacrificed to collect samples and calculate the spleen index and thymus weight index, HE staining was used to detect the pathology changes of stomach, ELISA was employed to assay the serum and spleen concentration of acid phosphatase(ACP) and N- acetyl-β-D- glucosaminidase(NAG).Results 1. Long-term OME administration can lead mouse spleen weight index and thymus index decreased. Compared with simple control group, low dose OME group spleen weight index declined, but the difference was not statistically significant; high dose OME group spleen weight index also decreased, the difference was statistically significant(P <0.05). Compared with MNNG group, MNNG + low dose OME group, MNNG + high dose OME group spleen weight index decreased, the differences were statistically significant(P <0.01). 2. Comparison with simple control group, OME group the fore-stomach did not change significantly, glandular mucosa folds shallow. MNNG group, MNNG + low dose OME group, MNNG +high dose OME group fore-stomach mucosal surface shows a large number of different sizes of white mice projections(maximum diameter of about 0.5cm), papillary protruding into the stomach cavity, partially visible ulcerative lesions; mice mucosal folds gland shallow, and some even disappear. Compared with MNNG group, MNNG + high-dose OME group fore-stomach carcinoma were significantly higher(P <0.05). Showed that Long-term high doses of OME administration of can promote MNNG-induced gastric cancer in mice. 3. OME group the serum and spleen ACP and NAG of mice were reduced, high-dose OME group compared with simple control group was significantly lower(P <0.05); Compared with MNNG group, MNNG + high doses OME group can significantly reduce serum and spleen ACP and NAG of mice(P <0.01)Conclusion OME can contribute to MNNG-induced gastric cancer in mice. The mechanism may be relate to inhibit lysosomal hydrolase enzyme and its functions and showing a dose-dependent trend, thereby reducing related to immune function in mice. |
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