亚硒酸钠对胃癌形成的作用及对bcl-2和Bax表达的影响

Effect of Na_2SeO_3 on bcl-2 and Bax expression and on gastric carcinogenesis in Wistar rats

目的 :探讨在胃癌形成过程中亚硒酸钠的作用机制及其对bcl 2和Bax蛋白表达的影响。方法 :用N甲基 -N -硝基 -N亚硝胍 (MNNG)2 0mg/kg给大鼠灌胃 ,以诱导大鼠胃腺癌形成。实验第 43周 ,用HE染色、病理诊断和AB PAS反应方法比较各组MNNG诱导Wistar大鼠腺胃癌形成过程中的变化 ;用免疫组织化学SP法观察在此过程中胃黏膜bcl 2和Bax蛋白表达 ,并对其结果进行定性、定位及图象分析。结果 :饮水中加入2和 4mg/L的亚硒酸钠加重胃黏膜的糜烂、出血和肠化生 ,P <0 0 5 ,在MNNG诱癌过程中发生了浆膜下平滑肌瘤 ,亚硒酸钠可增加平滑肌瘤的发生率。免疫组织化学结果显示 ,加硒组bcl 2阳性标本的平均光密度比正常对照组明显升高 ,P <0 0 1;加硒组的Bax平均光密度明显高于对照组 ,P <0 0 1。结论 :亚硒酸钠可增强大鼠胃黏膜bcl 2和Bax蛋白的表达 ,并使之糜烂、出血、肠化生 ;同时 ,可促进浆膜下平滑肌瘤的形成。

OBJECTIVE:To investigate the effect of Na 2SeO 3 on bcl-2 and Bax expression and on gastric carcinogenesis in Wistar rats. METHODS: Wistar rats were divided into four groups randomly:the high selenium group (4 mg/L), low selenium (2 mg/L) group, experiment control group and normal control group. The Wistar rat gastric cancer was induced by MNNG (20 mg/kg) gavage daily for 10 days. Na 2SeO 3 was fed by piped drinking before one week of MNNG (20 mg/kg) gavage. The Wistar rats were sacrificed at the 43th week. The surface characters of gastric mucosa were observed by naked eyes. Histopathologic changes were observed with HE staining and AB-PAS. Changes of bcl-2 and Bax protein were detected by SP immunohistochemical method. The immunohistochemical results were given situated and quantitative analysis by image analysis.RESULTS: Dietary Na 2SeO 3 (2 mg/L, 4 mg/L) aggravated gastric erosion and hemorrhage and promoted intestinal metaplasia of gastric mucosa,P<0.05,especially high selenium. The liomyoma was formed in gastric carcinogenesis which induced by N-methyl-N’-nitro-N-nitroso guanidine. Dietary Na 2SeO 3(2 mg/L, 4 mg/L) increased incidence of liomyoma. In bcl-2 immunohistochemical positive cells the mean optical density (MOD) was significantly increased in dietary selenium compared with the normal control group .The mean optical density (MOD) of Bax was significantly increased in dietary selenium compared with the normal control and experimental control groups,P<0.01.CONCLUSIONS:Dietary Na 2SeO 3 by piped drinking may regulate expression of bcl-2 and Bax protein. Thus imbalance bcl-2 and Bax protein may induce gastric erosion, hemorrhage and intestinal metaplasia of gastric mucosa.