MNNG诱导大鼠胃癌中亚硒酸钠和胃黏膜内分泌细胞的作用

Influence of Na_2SeO_3 and gastric endocrine cells on MNNG induced gastric carcinogenesis in rats

目的:探讨N甲基-N-硝基-N亚硝胍(MNNG)诱导Wistar 大鼠胃癌形成过程中亚硒酸钠和胃黏膜内分泌细胞的作用. 方法:用MNNG(20 mg/kg)诱导大鼠胃癌形成.用HE染色、显微镜观察和AB-PAS方法比较了硒在MNNG诱导大鼠胃癌形成过程中的作用,用免疫组织化学SP法研究在此过程中胃黏膜内P物质(SP)、胃泌素(GAS)和生长抑素(SOM) 阳性细胞的免疫组织化学变化,并对以上结果进行定性、定位、图像分析和统计学处理. 结果:饮水中加入2 mg/L和4 mg/L的亚硒酸钠加重胃黏膜糜烂、出血,促进胃黏膜肠上皮化生(45.5%,66.7%, 92.9%;92.9%vs 45.5%,P<0.05),在MNNG诱癌过程中发生了浆膜下平滑肌瘤,亚硒酸钠可以增加平滑肌瘤的发生率.胃黏膜内P物质阳性细胞的面数密度(NA)低硒组比正常对照组显著升高(9.909±5.665 vs 4.455±2.583, P<0.05);GAS阳性细胞的吸光度(Amean)实验对照组和低硒组显著低于正常对照组(0.187±0.033,0.119±0.024 vs 0.306±0.011,P<0.01),低硒组显著低于实验对照组(0.119±0.024 vs 0.187±0.033,P<0.01);SOM阳性细胞的NA和Amean各组之间无显著性差异. 结论:在MNNG所致胃癌形成过程中亚硒酸钠并不能降低大鼠胃癌的发生率;其机制可能与硒促进SP阳性细胞的增生和抑制G细胞的分泌功能有关.

AIM: To investigate influence of Na2SeO3 and gastric endocrine cells on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in rats and its mechanism. METHODS: Weaning male Wistar rats were divided randomly into four groups: The normal control group, experiment control group, low selenium (2 mg/L) group and high selenium group (4 mg/L). The Wistar rat gastric cancer was induced by MNNG (20 mg/kg) gavage daily for 10 days. Na2SeO3 was given by piped drinking before one week of MNNG (20 mg/kg) gavage. The Wistar rats were killed at the 43th week. The surface characters of gastric mucosa were observed with nude eyes. Histopathologic changes were observed by HE stain and AB-PAS methods. Changes of gastric endocrine cells were detected by immunohis-tochemical S-P method. The immunohistochemical results were quantitatively analyzed by the image analyzer. Statistical analysis was taken by SPSS. RESULTS: Dietary Na2SeO3 (2 mg/L, 4 mg/L) aggravated gastric erosion and hemorrhage and promoted intestinal metaplasia of gastric mucosa (45.5%, 66.7%, 92.9%; 92.9% vs 545.5%, P<0.05). Leiomyoma formed in the process of induced rats gastric carcinoma. Dietary Na2SeO3(2 mg/L, 4 mg/L) increased incidence rate of leiomyoma. The nu meric density of area (NA)of SP immunohistochemical positive cells was significantly increased in low selenium group than those of normal control group (9.909±5.665 vs 4.455±2.583, P <0.05). Absorbance mean (Amean) of gastrin immunohistochemical positive cells was significantly decreased in experimental control group, low selenium than that of normal control group (0.187±0.033, 0.119±0.024 vs 0.306±0.011, P<0.01), and low selenium group than experiment control group (0.119±0.024 vs 0.187±0.033, P<0.01). NA and Amean of somatostation cells (SOM) were not significantly different in each group. CONCLUSION: These findings suggested that dietary Na2SeO3 by piped drinking might not decrease incidence of Wistar rat gastric caner induced by MNNG. The mechanism may be involved in that selenium promoted SP cells proliferation and decreased secretion of gastrin cells in gastric mucosa.