前列腺素D2在小鼠溃疡性结肠炎癌变模型中的作用探讨

The role of prostaglandin D2 in the mice model of ulcerative colitis associated carcinogenesis

目的研究前列腺素D2(prostaglandin D2,PGD2)在实验性小鼠溃疡性结肠炎(ulcerative colitis,UC)癌变过程中的可能作用,并探讨其D类前列腺素受体1(D prostanoid receptor 1,DP1)拮抗剂(BWA868c)对癌变的可能预防作用。方法以经典氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)法建立小鼠UC相关癌变(UC associated carcinogenesis,UCAC)模型,并分为空白对照组(Con组)、模型对照组(AOM-Con组)、环氧合酶2抑制剂组(COX-2组)和DP1拮抗剂组(DP1组),评估小鼠的疾病活动指数(DAI)、结肠大体损伤及病理改变,ELISA法检测PGD2,Western blotting法检测COX-2、β-连环蛋白(β-catenin)的表达。结果AOM-Con组小鼠DAI升高,结肠可见多发隆起,病理以低级别或高级别上皮内瘤变为主,而COX-2组和DP1组的DAI评分、结肠损伤及β-catenin的表达均明显低于AOM-Con组(P<0.05);DP1组COX-2的表达与AOM-Con组相比,差异无统计学意义(P>0.05)。结论小鼠UCAC模型中的结肠黏膜异型增生可能与PGD2相关;DP1拮抗剂对UC癌变可起到化学预防作用。

Objective To investigate the possible role of prostaglandin D2(PGD2)in the carcinogenesis of experimental ulcerative colitis(UC)in mice,and to explore the possible preventive effect of its D prostanoid receptor 1(DP1)antagonist(BWA868c)on carcinogenesis.Methods The UC associated carcinogenesis(UCAC)mice model was established by the classic Azoxymethane/Dextran sodium sulfate(AOM/DSS)method and divided into blank control group(Con group),model control group(AOM-Con group),cyclooxygenase 2 inhibitor group(COX-2 group),and DP1 antagonist group(DP1 group).During the experiment,the disease activity index(DAI)of mice was evaluated,the general damage and pathological changes of colon tissue were observed,the expression of PGD2 in colon tissue was detected by ELISA method,and the expressions of COX-2 andβ-catenin were detected by Western blotting method.Results DAI in the AOM-Con group increased,multiple polypoid bulging lesions were visible to the naked eye of the colon,and the pathological changes were mainly low-grade or high-grade intraepithelial neoplasia.The DAI score,colon injury,andβ-catenin expression in the COX-2 group and DP1 group were all significantly lower than those in the AOMCon group(P<0.05);the expression of COX-2 in the DP1 group was not significantly different than that in the AOMCon group(P>0.05).Conclusion Colonic dysplasia of mice UCAC may be related to PGD2;DP1 antagonists can play a chemopreventive role in UC carcinogenesis.