摘要
目的研究非类固醇抗炎药物苏灵大对Ｎ甲基Ｎ亚硝基脲（ＭＮＵ）诱导小鼠大肠肿瘤的抑制作用，探讨苏灵大对大肠肿瘤的化学性预防作用及其作用机理．方法采用ＭＮＵ直肠内灌注诱导小鼠大肠癌模型．在第１实验中自第１周起诱癌组和对照组同时给予直肠内灌注ＭＮＵ（４ｇ／Ｌ，０４ｍｌ３次／周×６周，１次／周×６周）１２周和口服苏灵大液体（７５ｍｇ／Ｌ）１８周；在第２实验中，小鼠先给予ＭＮＵ直肠内灌注１２周，而后随机分为苏灵大组和对照组，苏灵大组小鼠给予口服含苏灵大液体１８周．在各实验结束时处死各组小鼠，观察和计数结肠内肿瘤数量，测量平均肿瘤直径和平均肿瘤体积，观察诱导肿瘤的组织形态学特征．结果诱导的肿瘤均位于大肠的远端，形态可分为粟粒型、溃疡型和粘膜增厚型．苏灵大组和对照组在诱导的小鼠大肠肿瘤部位分布和肿瘤大体形态方面没有显著性差异．在诱导出现肿瘤的结肠全层席卷组织切片上，第１实验中苏灵大组平均腺瘤数量（８４）明显高于对照组（４７），腺癌平均数量（３９）低于对照组（９３）；而在第２实验中两组间没有明显的差异性．第１实验中，苏灵大组诱导出现肿瘤的小鼠数量（苏灵大组３７５％，对照组７９２％）、肿瘤灶数量（苏灵大组?
AIM To investigate the chemopreventive effect of Sulindac, one of the nonsteroid anti inflammatory drugs, on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors. METHODS The experimental colonic tumor model in mice induced by intrarectal instillation of MNU was used. In the first experiment, intrarectal MNU was installated (4g/L, 0 4ml 3 times a week for 6 weeks and then once a week for the following 6 weeks) and Sulindac (7 5mg/L) was administered concurrently for 18 weeks, while a control group of animals received MNU only for the same period. In the second experiment, two groups of mice which had already been treated with MNU for 12 weeks received either Sulindac or not for another 12 weeks. RESULTS The induced tumors in mice were all located in the distal part of the large intestine. There were no significant differences in the location and the gross appearance of the tumor in the MNU induced group and control group both in the first and the second experiment. In the first experiment, Sulindac lowered significantly both the number of mice with colonic tumors (Sulindac group 37 5%, control 79 2%) and the number of tumors per group (Sulindac group 9, control group 17). Sulindac had a significant inhibitive effect on the growth of the MNU induced tumors. However, in the second experiment the inhibitive effect of Sulindac was lessened or disappeared. CONCLUSION Sulindac has a protective effect against the chemical induction of colonic tumors by MNU in mice. The chemopreventive effect was more significant in the initiation stage of the tumor, while in the promotion stage this effect was lessened or disappeared. Sulindac could not cause the regression of established tumors.
关键词
苏灵大
甲基亚硝基脲
大肠肿瘤
Colorectal neoplasms/pathology Sulindac Adenocarcinoma Nitrosourea compounds
