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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 detect the dynamic changes of DNA methyltransferase (DNMT) and DNA demethylation transferase in the pathological course of colorectal cancer in mice treated with azodicarbonamide / dextran sodium sulfate and to explore the pathogenesis of colitis-associated colon cancer (CAC) Mechanism and Chinese medicine intervention mechanism. Method: intraperitoneal injection of azoxymethane (AOM) + libitum for three cycles of dextran sulfate sodium (DSS water) to establish a mouse model of colitis-associated colon, real-time quantitative PCR (real time PCR) detection of colitis-associated colorectal The expression of DNMT3a, TET3 and TDGmRNA in colorectal cancer tissues of different pathological stages were detected by Western blot. Results: At 5 weeks (pathology: inflammation), DNMT3A expression decreased and TET3 and TDG expression increased in model group. At 8 weeks (pathology: moderate to severe dysplasia and adenocarcinoma), model DNMT3A group methylase increased expression of demethylase TET3 expression decreased, demethylase TDG expression is still elevated. At 5 weeks, DNMT3a expression was increased and TET3 and TDG expression were decreased at 5 weeks after SAH + Patrinia (15g / kg) or sulfasalazine (0.75g / kg) treatment. At 8 weeks, DNMT3A expression decreased and TET3 expression Increased, TDG expression decreased. Conclusion: The changes of DNA methylation / DNA demethylation may be related to the process of inflammatory transformation to carcinogenesis in colitis-associated colon cancer model mice. To some extent, this balance of DNA methylation / DNA demethylation is reversed, potentially interfering with colitis-cancer pathology.