慢性肠道炎症促进肝癌的发展

发布时间：2018-11-14 19:05

【摘要】：目的探讨慢性肠道炎症状态下菌群结构及构成改变对肝癌进展的影响。方法 22只雄性乙肝病毒转基因小鼠在出生后第2周腹腔注射二乙基亚硝胺诱导小鼠原发性肝癌,随机分为慢性肠炎组(给予含2%葡聚糖硫酸钠的饮用水)和对照组(给予正常饮用水)。上述小鼠观察至22周龄。在此期间定期进行肝功能测定,收集粪便进行宏基因组测序。另将4只已发生肝癌的小鼠与7只8周龄肉眼及病理学未见肝癌的小鼠同笼(分2笼)饲养16周。结果 DSS所诱导的慢性肠炎小鼠与正常饮用水小鼠相比肝功能无显著改变;DSS诱导的慢性肠炎组小鼠(n=10)在第22周龄时有9只发生弥漫性肉眼可见的肝癌,而正常饮用水小鼠(n=12)仅有2只发生肝癌,肿瘤发生率(P=0.002)和肿瘤数量(P=0.028)有显著差别;与正常饮用水小鼠相比,慢性肠炎组小鼠肠道菌群中,普雷沃氏菌属(P=0.022)和厌氧支原体属(P=0.014)显著减少;与已发生肝癌小鼠进行同笼饲养的小鼠(n=7)在24周龄时全部发生肉眼可见的肝癌。结论慢性肠道炎症状态下,肠道菌群改变可促进肝癌进展。
[Abstract]:Objective to investigate the effect of microflora structure and composition on the progression of hepatocellular carcinoma (HCC) under chronic intestinal inflammation. Methods 22 male HBV transgenic mice were intraperitoneally injected with diethylnitrosamine at the second week after birth to induce primary liver cancer in mice. They were randomly divided into chronic enteritis group (drinking water containing 2% dextran sulfate) and control group (normal drinking water). The above mentioned mice were observed to be 22 weeks old. During this period, liver function was measured regularly, and stool samples were collected for macro genome sequencing. In addition, 4 mice with liver cancer were fed with 7 mice aged 8 weeks without liver cancer in the same cage (divided into 2 cages) for 16 weeks. Results there was no significant change in liver function in DSS induced chronic enteritis mice compared with normal drinking water mice. In DSS induced chronic enteritis group (NN10), 9 mice developed diffuse hepatocellular carcinoma at the age of 22 weeks, while only 2 mice with normal drinking water (NM12) developed HCC. There were significant differences in tumor incidence (P0. 002) and tumor number (P0. 028). Compared with the normal drinking water mice, the intestinal flora of mice with chronic enteritis was significantly lower than that of the mice with chronic enteritis (P0. 022) and anaerobic mycoplasma (P0. 014). All the mice fed with the same cage (nong7) at the age of 24 weeks developed HCC visible to the naked eye. Conclusion the change of intestinal flora can promote the progression of liver cancer under chronic intestinal inflammation.
【作者单位】：广州医科大学;中国医学科学院肿瘤医院分子肿瘤学国家重点实验室;中国医学科学院肿瘤医院影像诊断科;中国医学科学院肿瘤医院放射治疗科;
【基金】：973课题“细胞微环境在肿瘤发生发展及侵袭转移中的作用及机制”(2011CB504205)
【分类号】：R735.7;R574

【共引文献】