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丁酸盐灌肠剂在实验性结肠炎及大鼠模型中对大肠癌的预防作用

Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model.

作者信息

D'Argenio G, Cosenza V, Delle Cave M, Iovino P, Delle Valle N, Lombardi G, Mazzacca G

机构信息

Gastrointestinal Unit, School of Medicine, Federico II University, Naples, Italy.

出版信息

Gastroenterology. 1996 Jun;110(6):1727-34. doi: 10.1053/gast.1996.v110.pm8964397.

DOI:10.1053/gast.1996.v110.pm8964397
PMID:8964397
Abstract

BACKGROUND & AIMS: Butyrate is effective in experimental colitis by increasing transglutaminase activity. Because ulcerative colitis increases the risk of colonic neoplasia, the aim of this study was to investigate whether butyrate treatment reduces mucosal sensitivity to colon cancer development in rats with experimental colitis.

METHODS

Colon cancer was induced by azoxymethane injections in 10 rats with trinitrobenzensulfonic acid-induced colitis and 10 rats without colitis. Three additional groups of rats with colitis were treated with butyrate, mesalamine, and saline enemas, respectively, twice daily for 8 weeks; 1 week after colitis induction, tumors were induced. Biopsy specimens for assessment of proliferation pattern and transglutaminase activity were obtained during the latent period of cancer development. Characteristics of tumors were recorded 27 weeks after the first exposure to azoxymethane.

RESULTS

Experimental colitis enhanced carcinogenesis; butyrate therapy reduced both incidence and size of tumors and also affected colonic proliferation pattern. Transglutaminase levels were restored by butyrate treatment in rats with colitis.

CONCLUSIONS

The protective effect of butyrate against large bowel cancer in experimental colitis suggests its usefulness in long-term therapy to decrease disease relapses and to reduce colon cancer risk in ulcerative colitis.

摘要

背景与目的

丁酸盐可通过提高转谷氨酰胺酶活性对实验性结肠炎产生疗效。鉴于溃疡性结肠炎会增加结肠肿瘤形成的风险,本研究旨在探讨丁酸盐治疗是否能降低实验性结肠炎大鼠对结肠癌发生的黏膜敏感性。

方法

给10只三硝基苯磺酸诱导的结肠炎大鼠和10只未患结肠炎的大鼠注射氧化偶氮甲烷诱导结肠癌。另外三组结肠炎大鼠分别用丁酸盐、美沙拉嗪和生理盐水灌肠治疗,每天两次,共8周;在诱导结肠炎1周后诱导肿瘤形成。在癌症发展的潜伏期获取活检标本以评估增殖模式和转谷氨酰胺酶活性。在首次接触氧化偶氮甲烷27周后记录肿瘤特征。

结果

实验性结肠炎增强了致癌作用;丁酸盐治疗降低了肿瘤的发生率和大小,还影响了结肠增殖模式。丁酸盐治疗使结肠炎大鼠的转谷氨酰胺酶水平恢复正常。

结论

丁酸盐对实验性结肠炎中大肠癌的保护作用表明,其在长期治疗中有助于减少疾病复发并降低溃疡性结肠炎患者患结肠癌的风险。

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