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AOM/DSS小鼠结肠DNA甲基化/去甲基化酶的动态变化及救必应加败酱草的干预

Dynamic change of DNA methylase and DNA demcthylase in AOM/DSS mouse colon and the intervention of heat clearing and detoxifying drugs
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摘要 目的:检测氧化偶氮甲烷/葡聚糖硫酸钠小鼠结肠炎癌病理进程中DNA甲基化转移酶和DNA去甲基化转移酶的动态变化,探讨结肠炎相关结肠癌(CAC)的发病机理及中药干预机制。方法:采用腹腔注射氧化偶氮甲烷(AOM)+三个循环自由饮用葡聚糖硫酸钠(DSS水)建立结肠炎相关结肠癌小鼠模型,实时定量PCR(real time PCR)检测结肠炎相关结肠癌模型小鼠不同病理阶段结肠组织DNMT3a、TET3、TDGmRNA表达;采用Western blot法检测上述组织对应蛋白表达水平。结果:5周时(病理:炎症),模型组甲基化酶DNMT3A表达降低而去甲基化酶TET3、TDG表达升高;8周时(病理:中重度异型增生和腺癌形成),模型组甲基化酶DNMT3A表达升高而去甲基化酶TET3表达降低,去甲基化酶TDG表达仍升高。经救必应+败酱草(15g/kg)或柳氮磺吡啶(0.75g/kg)治疗后,5周时DNMT3a表达升高而TET3、TDG表达降低,8周时DNMT3A表达降低而TET3表达升高,TDG表达降低。结论:DNA甲基化/DNA去甲基化平衡的改变可能与结肠炎相关结肠癌模型小鼠由炎症向癌变转化的过程有关;救必应+败酱草、柳氮磺吡啶均可在一定程度上逆转这种DNA甲基化/DNA去甲基化平衡的改变,从而可能干预结肠炎-癌病理进程。 Objective:To investigate the dynamic change of DNA methylase and DNA demethylase in the onset of colitis carcinoma of AOM/DSS mouse, to analysis pathogenesis of colitis-associated cancer ( CAC ) as well as the intervention mechanism of Traditional Chinese medicine. Methods :The CAC models were established by a single abdomen injection of chemical carcinogen azoxymethane(AOM) combined with three cycles free drinking of dextran sulfate sodium salt reagent grade(DSS). The expression levels of DNMT3a ,TET3 ,TDG mRNA in colon of mice were detected by real time polymerase chain reaction (RT-PCR). The expression of DNMT3a, TET3, TDG at protein level by Western blot. Results:In fifth weeks (pathology:inflammation) :Compared to normal controls, the expression of DNMT3a in model group decreased, whereas TET3 ,TDG in model group increased. In eighth week( pathology:severe dysplasia ang adenocareinoma formation) :Compared to normal controls, the expression of DNMT3a in model group increased, whereas TET3 decreased, TDG increased. After treatment of JB or SASP (25g/ kg) :the expression of DNMT3a increased, whereas TET3 ,TDG decreased in fifth weeks;the expression of DNMT3a decreased, whereas TET3 increased, TDG decreased in eighth weeks. Conclusion:The balance between DNA methylationand DNA demethylation may be related to the transformation from inflammation to colitis-associated cancer. Both JB and SASP can reverse the change, thus may intervene the progression from inflammation to colitis-associated cancer.
作者 钱彩云 覃景春 揭凤鸣 巫燕莉 杜群 李燕舞 Qian Caiyun1, Qin Jingchun1, Jie Fengming1 , Wu Yanli1, Du Qun1 , Li Yanwu1 (Pi Wei Institution , Guangzhou University of Traditional Chinese Medicine, Guangzhou 510000)
出处 《中药药理与临床》 CSCD 北大核心 2017年第3期138-142,共5页 Pharmacology and Clinics of Chinese Materia Medica
基金 "华南中医药协同创新中心-中医药防治脾胃病、脑病创新研究团队"项目(A1-AFD01514A05) "广州中医药大学薪火计划"项目(A1-AFD015141Z0234)
关键词 救必应+败酱草 结肠炎相关结肠癌(CAC) DNA甲基化 DNA去甲基化 JB (救必应+败酱草) Colitis-associated cancer DNA methylation DNA demethylation
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