奥美拉唑促小鼠胃癌发生的机制研究  

Study on the mechanism of omeprazole in promoting the development of gastric cancer in mice

作　　者：何伟[1] 齐东江 徐阿曼[1,2] 袁笑[1] 陆震[1] 

机构地区：[1]安徽医科大学第四附属医院普外科,安徽合肥230032 [2]安徽医科大学第一附属医院胃肠外科一病区,安徽合肥230022

出　　处：《安徽医药》2016年第6期1054-1060,共7页Anhui Medical and Pharmaceutical Journal

摘　　要：目的：研究奥美拉唑（omeprazole，ome）是否会增加小鼠胃癌的发病率并探讨其可能存在的机制。方法实验分为单纯对照组、ome 低剂量组（6 mg·kg －1）、ome 高剂量组（30 mg·kg －1）、甲基硝基亚硝基胍（N-methyl-N＇-nitro-N-nitrosoguanidine， MNNG）组、MNNG ＋ome 低剂量组、MNNG ＋ome 高剂量组。MNNG 加入饮用水中（100 mg·L －1）小鼠自由饮用。每组7只小鼠，常规饲养24周后处死小鼠收集标本并计算小鼠脾质量指数，HE 染色观察小鼠胃病理形态学改变，ELISA 法检测小鼠血清及脾脏中酸性磷酸酶（acid phosphatase，ACP）、N-乙酰-β-D-氨基葡萄糖苷酶（N-acetyl-β-D-glucosaminidase，NAG）含量；Western Blotting 检测小鼠胃 p21、p53、mTOR 表达。结果ome 组与对照组相比及 MNNG 组与 ome ＋组相比，小鼠脾质量指数、血清及脾脏中溶酶体酶活性明显下降；与 MNNG 组相比 ome ＋组小鼠胃癌发生率明显增加，尤其是 MNNG ＋ome 高剂量组，两者差异有统计学意义（P ＜0．05）；和对照组相比，实验组 p53表达增加，p21表达减少，mTOR 表达减少，差异均有统计学意义（P ＜0．05）。结论ome 可以促进胃癌发生，其机制可能是和抑制小鼠体内溶酶体及其水解酶的活性，从而降低小鼠免疫功能有关。Objective To investigate if oral omeprazole（ome）will increase the incidence of gastric cancer in mice and the possible mechanism.Methods Mice were divided into 6 groups,with seven mice in each group,including control group,low-dose ome group,high-dose ome group,N-methyl-N＇-nitro-N-nitrosoguanidine （MNNG）group,MNNG ＋low-dose ome group （6 mg·kg -1 ）, and MNNG ＋high-dose ome group （30 mg·kg -1 ）.The mice were administrated with drinking water containing MNNG.The mice were raised in a routine way for 24 weeks.After that the mice were sacrificed to collect samples and calculate the mice spleen index. HE staining of the mice stomach was applied to exam the histological changes.Serum and spleen concentrations of acid phosphatase （ACP）and N-acetyl-β-D-glucosaminidase （NAG）were detected by ELISA.And the expression levels of p21,p53 and mTor in the mouse stomach were detected by Western Blotting.Results In the comparison of the ome group with the control group and the MNNG group with the ome ＋ group,mice spleen weight indexes in the ome group and the ome ＋ group decreased significantly. Meanwhile,mice serum and spleen lysosomal enzyme levels also decreased significantly.Compared with MNNG group,the incidence of gastric cancer in the ome ＋group was increased significantly.especially in the MNNG ＋ome high-dose group,.and the difference was statistically significant （P 〈0.05）.Compared with the control group,the expressions of p53 in the experimental group was in-creased,the expressions of p21 decreased,and the expressions of mTOR also decreased （P 〈0.05 ）.Conclusions Ome can pro-mote gastric carcinogenesis in mice,and its mechanism may be through the inhibition of lysosomal hydrolase enzyme and its fuction in mice,thereby reducing the immune fuction in these mice.

关 键 词：胃肿瘤 奥美拉唑 溶酶体 酸性磷酸酶 印迹法 蛋白质 小鼠 基因敲除 

分 类 号：R735.2[医药卫生—肿瘤]