5-氨基水杨酸在结肠炎癌变模型小鼠中的初步研究

Preliminary study on 5-aminosalicylic acid in a mouse model of colitis-associated carcinoma

目的应用5-氨基水杨酸（5-AsA）干预偶氮氧甲烷（AOM）联合葡聚糖硫酸钠（Dss）诱导小鼠结肠炎癌变的模型，观察结肠过氧化物酶体增殖物激活受体γ（PPAR-γ）、β-catenin的表达水平。方法36只BALB／c小鼠均分为对照组、模型组和干预组。模型组和干预组均于实验前1d予AOM10mg／kg腹腔注射，继以自由饮用4％DSS1周，再普通饮水2周，饮用DSS及普通饮水共重复3个循环。干预组于实验前3d予5-ASA150mg／kg饲喂至实验结束。对照组于实验前1d予0．9％NaCl溶液腹腔注射，普通饮水9周。监测小鼠疾病症状，评价实验1周末及9周末结肠组织学病理变化，检测9周末结肠PPAR-γ、β-catenin蛋白及结肠PPAR-γmRNA表达水平。统计学处理采用t检验。结果干预组饮用DSS1周后结肠炎疾病活动指数（DAD为1．81±0．59，9周末平均肿瘤数为4．11±1．05，均较模型组（DAI为2．47±0．53，肿瘤数为9．71±2．29）明显降低（t=2．88和6．55，P均〈0．01）。干预组结肠PPAR-γ蛋白（2．11±1．36）及mRNA（1．45±0．10）平均表达水平均较模型组（分别为0．43±0．53，0．5γ±0．08）明显增加（t=3．07和18．99，P均〈0．01）。各组间β—catenin表达差异无统计学意义（P〉0．05）。结论5-ASA有效减轻AOM和DSS诱导的小鼠结肠炎癌变模型的炎性反应及肿瘤负荷，同时促进PPAR-γ在结肠中的表达，而对结肠中B—catenin的表达无明显影响。

Objective To investigate the expressions of peroxisome proliferator activated receptor-γ （PPAR-γ） and β-catenin in 5-aminosalicylic acid （ASA） intervened colitis carcinogenesis mouse model induced by azoxymethane （AOM） and dextran sulfate sodium （DSS）. Methods Thirty-six BALB/c mice were evenly divided into control group, model group, and intervention group. For model group and intervention group, mice were intraperitoneally injected with AOM （10 mg/kg） one day before experiment, then drank 4% DSS solution freely for one week and followed with common drinking water for another two weeks. Taking 4 % DSS solution and common drinking water repeated for three cycles. For intervention group, 5-ASA （150 mg/kg） was given from three days before experiment to the end of research. For control group, mice were intraperitoneally injected with 0.9 % NaC1 solation and then given common drinking water for nine weeks. The symptoms of the disease were monitored in mice and pathological changes of tissues were evaluated at the end of first week and ninth week. At the end of the ninth week, the expressions of PPAR-γ, β-catenin protein and PPAR-γ at mRNA level in colon tissue were detected. The data were analyzed by t test. Results The colitis disease activity index （DAI） index of intervention group was 1.81 ~0.59 after drinking DSS solution for one week and the number of tumor was 4. 11 ± 1. 05 at the end of the ninth week, both were significantly lower than those of model group （2.47=k0.53 and 9.71±2.29 respectively, t=2.88 and 6.55;both P〈0.01）. The expression of PPAR-7 at protein level （2. 11 ± 1.36） and mRNA lvel （1.45± 0. 10） in colon tissue of intervention group significantly increased compared with those of model group （0.43±0.53 and 0. 57±0. 08 respectively, t=3.07 and 18.99, both P〈0.01）. There was no significant difference of β-catenin expression among groups （P〉0.05）. Conclusions 5-ASA can efficiently improve the inflammatory reaction and tumor load in AOM and DSS induced colitis carcinogenesis mouse model, and at the same time can promote the expression of PPAR-γ in colon. However, there was no significant influence on the expression of β-catenin.