尼美舒利对乙基硝基亚硝基胍诱导大鼠胃癌的化学预防作用  

Effect of nimesulide on chemoprevention of N-ethyl-N-nitro-N-nitrosoguanidine-induced gastric cancer in rat model

作　　者：张丽[1] 陆红[1] 刘文忠[1] 陈晓宇[1] 施尧[1] 萧树东[1] 

机构地区：[1]上海第二医科大学附属仁济医院上海市消化疾病研究所,200001

出　　处：《中华消化杂志》2003年第7期391-394,共4页Chinese Journal of Digestion

基　　金：上海市科委科技发展基金资助项目 (0 0XD14 0 0 3 ) ;上海市教委资助项目 (0 2BQ2 5 )

摘　　要：目的　探讨选择性环氧合酶 2 (COX 2 )抑制剂尼美舒利对乙基硝基亚硝基胍 (ENNG)诱发大鼠胃癌的化学预防作用。方法　 96只雄性Wistar大鼠分成 6组分别饮用不同药物 :阴性对照组 (P组 ,纯净水 )、胃癌模型组 (M组 )、尼美舒利小剂量干预组 (MNL 组 )和大剂量干预组 (MNH 组 )、尼美舒利小剂量对照组 (NL 组 )和大剂量对照组 (NH 组 )。喂养 (2 8± 2 )周后观察各组大鼠的胃黏膜病变。结果　 89只 (92 .7% )大鼠完成实验。M组大鼠胃癌发生率为 5 6 .3% (9/ 16 ) ,显著高于MNL 组的 7.4 %(1/ 14 )和MNH 组的 6 .3% (1/ 16 ,P <0 .0 1) ,但MNL 组和MNH 组之间胃癌发生率差异无显著性 (P >0 .0 5 ) ;P组、NL 组和NH 组均无胃癌发生。M组大鼠胃黏膜萎缩、肠化和异型增生发生率也显著高于MNL 组和MNH 组 (P <0 .0 5 )。M组、MNL 组和MNH 组胃黏膜COX 2蛋白表达的阳性率分别为6 8.7% (11/ 16 )、2 1.4 % (3/ 14 )和 12 .5 % (2 / 16 ,P <0 .0 1)。结论　选择性COX 2抑制剂尼美舒利能有效抑制ENNG诱导的大鼠胃癌及癌前状态的发生 ,这为COX 2抑制剂对人类胃癌有潜在化学预防作用提供了证据。Objective To investigate the effect of nimesulide,a selective cyclooxygenase (COX)-2 inhibitor,on the chemoprevention of N-ethyl-N-nitro-N-nitrosoguanidine (ENNG)-induced gastric cancer in rat model. Methods Ninety-six male Wistar rats were randomized to drink the solution of ENNG (group M), ENNG/low dose nimesulide (group MN_L), ENNG/ high dose nimesulide (group MN_H), low dose nimesulide (group N_L), high dose nimesulide (group N_H) or water (group P). Eighty-nine(92.7%) rats completed the study and were sacrificed at (28±2) weeks. The animals were assessed for the presence of gastric cancer, COX-2 expression and precancerous changes in gastric mucosa. Results The incidence of gastric carcinoma in group M was 56.3% (9 /16), significantly higher than 7.4%(1/14)in MN_L group and 6.3%(1/16)in MN_H group( P < 0.01 ). No cancer occurred in P, N_L or N_H groups.The incidences of gastric mucosal atrophy, intestinal metaplasia and dysplasia in M group were significantly higher than those in MN_L group or MN_H group( P <0.05).The positive rates of COX-2 protein in M、MN_L and MN_H groups were 68.7% (11/16), 21.4% (3/14) and 12.5% (2/16) respectively( P <0.01). Conclusions The selective COX-2 inhibitor nimesulide can significantly inhibit development of gastric cancer and precancerous changes induced by ENNG in model of rat. This provides evidence that COX-2 inhibitors may have chemopreventive potential in human gastric cancer.

关 键 词：尼美舒利 乙基硝基亚硝基胍 诱导 大鼠 胃癌 化学预防 选择性环氧合酶-2抑制剂 胃黏膜萎缩 癌前状态 

分 类 号：R735.2[医药卫生—肿瘤]