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N-甲基-N'-硝基-N-亚硝基胍诱导大鼠上消化道癌变及十二指肠内容物反流的研究

Carcinogenesis of the upper gastrointestinal tract induced by N-methyl-N'-nitro-nitrosoguanidine and reflux of duodenal contents in the rat.

作者信息

Naresse Luiz Eduardo, Kobayasi Shoiti, Rodrigues Maria Aparecida Marchesan

机构信息

Department of Surgery and Orthopedics, Botucatu Medical School, UNESP, Sao Paulo, Brazil.

出版信息

Acta Cir Bras. 2009 Mar-Apr;24(2):112-7. doi: 10.1590/s0102-86502009000200007.

DOI:10.1590/s0102-86502009000200007
PMID:19377779
Abstract

PURPOSE

To investigate the combined effects of reflux of duodenal contents through the pylorus and treatment with N-methyl-N'-nitro-nitrosoguanidine (MNNG) on the development of lesions in the glandular stomach, at the gastrojejunal anastomosis and in the forestomach of rats.

METHODS

Eighty Male Wistar rats were divided into 4 groups: G1: MNNG + Reflux, G2: Reflux, G3: MNNG and G4: Gastrostomy. MNNG was given in the drinking water (100 mg/ml) for 12 weeks and then two groups (G1 and G2) were submitted to a gastrojejunal anastomosis followed by section of the afferent loop and suture of both stumps to allow reflux of duodenal contents through the pylorus. The animals were sacrificed 18 and 36 weeks after surgery. The lesions obtained in the antral mucosa, at the gastrojejunal anastomosis and in the forestomach were analysed histologically.

RESULTS

Duodenal reflux induced proliferative lesions at both glandular and squamous mucosa of the stomach. In the antrum, adenomatous hyperplasia (AH) was observed in 20% and 50% of the animals at the 18th and 36th weeks respectively. Aditionally 85% of the animals presented AH at the gastrojejunal anastomosis and 60% developed squamous hyperplasia at the squamous portion of the stomach. MNNG treatment plus duodenal reflux enhanced the development of malignant tumors at both glandular and squamous mucosa, since there were 30% of antral adenocarcinomas and 45% of squamous carcinomas at the 18th week and the frequency of these malignant tumors rose to 50% in the antrum and 65% in the squamous mucosa at the 36th week.

CONCLUSION

The reflux of duodenal contents through the pylorus enhanced the development of proliferative lesions, benign and malignant, in the glandular stomach and in the forestomach of rats.

摘要

目的

研究十二指肠内容物经幽门反流与N-甲基-N'-硝基-亚硝基胍(MNNG)处理对大鼠腺胃、胃空肠吻合口及前胃病变发展的联合影响。

方法

80只雄性Wistar大鼠分为4组:G1:MNNG + 反流组;G2:反流组;G3:MNNG组;G4:胃造口术组。MNNG以100 mg/ml的浓度溶于饮用水中,持续给予12周,然后对两组(G1和G2)进行胃空肠吻合术,随后切断输入袢并缝合两端残端,以使十二指肠内容物经幽门反流。术后18周和36周处死动物。对胃窦黏膜、胃空肠吻合口及前胃的病变进行组织学分析。

结果

十二指肠反流在胃的腺性和鳞状黏膜均诱发了增殖性病变。在胃窦,分别在第18周和第36周,20%和50%的动物出现腺瘤样增生(AH)。此外,85%的动物在胃空肠吻合口处出现AH,60%的动物在胃的鳞状部分出现鳞状上皮增生。MNNG处理加十二指肠反流增强了腺性和鳞状黏膜恶性肿瘤的发生,因为在第18周有30%的胃窦腺癌和45%的鳞状细胞癌,而在第36周,这些恶性肿瘤在胃窦的发生率升至50%,在鳞状黏膜的发生率升至65%。

结论

十二指肠内容物经幽门反流促进了大鼠腺胃和前胃增殖性病变(良性和恶性)的发展。

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