尼美舒利抑制乙基硝基亚硝基胍诱导大鼠胃癌癌前病变的作用机制  

Inhibitory effect of nimesulide on the development of N-ethyl-N-nitro-N-nitrosoguanidine-induced gastric precancerous lesions in rats

作　　者：张丽[1] 刘文忠[2] 陆红[2] 陈晓宇[2] 彭延申[2] 

机构地区：[1]江苏省昆山市第一人民医院消化科,江苏省昆山市215300 [2]上海交通大学附属仁济医院消化所,上海市100080

出　　处：《世界华人消化杂志》2012年第5期405-409,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨选择性环氧合酶-2(COX-2)抑制剂尼美舒利在乙基硝基亚硝基胍(ENNG)诱导大鼠胃癌癌前病变发展过程的作用以及可能机制.方法:6周龄♂Wistar大鼠给予浓度为100 mg/L的ENNG溶液饮用14 wk后,使用浓度为300 m g/L和1 200 mg/L的尼美舒利溶液由大鼠自由饮用,分别在喂养14、26和38 wk后观察大鼠胃黏膜病变.使用免疫组织化学的方法观察大鼠病变胃黏膜COX-2蛋白、Bcl-2蛋白以及PCNA的表达,TUNEL法检测大鼠胃黏膜细胞凋亡.结果:药物干预的大鼠胃癌癌前病变的发生率显著低于对应的非用药组(P<0.05);药物干预组大鼠病变胃黏膜的COX-2蛋白和Bcl-2蛋白表达分别为17.6%,35.3%,显著低于非用药组的60%和84%(P<0.05);增殖指数18.9±4.57显著低于非用药组49.43±7.92(P<0.05);凋亡指数13.6±1.82显著高于非用药组2.12±0.53(P<0.05);COX-2蛋白和Bcl-2蛋白与PCNA的表达以及凋亡指数具有相关性(P<0.01).结论:选择性COX-2抑制剂尼美舒利能有效抑制ENNG诱导的大鼠胃癌癌前病变的发展,其机制可能是通过抑制COX-2、Bcl-2蛋白的表达,从而抑制病变胃黏膜细胞的增殖以及诱导其凋亡.METHODS： Six-week-old male Wistar rats were given 100 mg/L of ENNG in their drinking water for 14 wk and then fed a diet containing nimesulide at doses of 300 mg/L and 1200 mg/ L for 12 or 24 wk. The rats were sacrificed 14, 26 and 38 wk after nimesulide feeding to detect the changes in the gastric mucosa. The expres-sion of COX-2, Bcl-2 and PCNA in the gastric mucosa was detected by immunohitochemistry, and cell apoptosis was determined using TU- NEL assay.RESULTS： Nimesulide significantly reduced the incidence of gastric precancerous lesions compared to controls （P 〈 0.05）. The positive rates of COX-2 and Bcl-2 protein expression and proliferation index in the nimesulde group were significantly lower than those in the control group （17.6% vs 60%, 35.3% vs 84%, 18.9 ± 4.57 vs 49.43 ± 7.92, all P 〈 0.05）, while the apoptotic index was significantly higher in the nimesulde group than in the control group （13.6 ± 1.82 vs 2.12 ± 0.53, P 〈 0.05）. The expression of COX-2 and Bcl-2 protein was associated with prolifera- tion index and apoptotic index （P 〈 0.01）.CONCLUSION： Nimesulide has inhibitory effects on the development of ENNG-induced gastric precancerous lesions in rats possibly via mechanisms associated with reducing COX-2 and Bcl-2 expression, inhibiting proliferation and inducing apoptosis of gastric epithelial cells.

关 键 词：尼美舒利 对乙基硝基亚硝基胍 胃癌癌前病变 

分 类 号：R735.2[医药卫生—肿瘤]