Faecalibacteriu mprausnitzii在结肠炎相关结直肠癌发生中的作用

Effect of Faecalibacterium prausnitzii in Colitis-associated Colorectal Cancer

背景:Faecalibacterium prausnitzii(Fp)是人类肠道中数量最占优势的细菌之一,与结肠炎相关结直肠癌(CAC)的发生密切相关。目的:研究Fp对CAC发生的影响,并初步探讨可能的机制。方法:应用氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导CAC模型,将52只C57BL/6J小鼠随机分为A组(AOM+DSS)、B组(AOM+DSS+Fp)、C组(AOM+DSS+Fp上清)、D组(空白对照),第92天处死小鼠。评估DAI,ELISA法检测血清TNF-α和IL-10含量;HE染色观察肿瘤分级;免疫组化法检测肠道肿瘤组织中VEGF、COX-2、NF-κB表达。结果:A、B、C组小鼠成瘤率分别为100%、100%和77.8%,主要为高级别上皮内瘤变。A组肿瘤负荷显著高于B组(P<0.01),B组脾脏指数显著高于C组(P<0.01)。A组血清TNF-α含量显著低于B组(P<0.05),IL-10显著升高(P<0.05)。A、B、C组肠道肿瘤组织中VEGF、COX-2、NF-κB表达无明显差异。结论:Fp活菌对实验性小鼠肠道肿瘤的发生率无明显影响,而其上清能减少肿瘤发生率。Fp活菌及其上清均可能通过调节TNF-α、IL-10表达来减轻肠道肿瘤负荷。

Background： Faecalibacterium prausnitzii（ Fp） is one of the most abundant bacterium in human intestinal microbiota,and is closely correlated with the process of colitis-associated colorectal cancer（ CAC）. Aims： To observe the effect of Fp on CAC,and investigate the possible mechanism. Methods： The model of CAC was induced by azoxymethane（ AOM） and dextran sodium sulfate（ DSS）. Fifty-two C57BL/6J mice were randomly divided into 4 groups： group A（ AOM ＋ DSS）,group B（ AOM ＋ DSS ＋ Fp）,group C（ AOM ＋ DSS ＋ Fp supernatant） and group D（ control group）. All the mice were sacrificed on day 92. DAI was assessed,serum levels of TNF-α and IL-10 were determined by ELISA. HE staining was used to examine the grade of tumor. Expressions of VEGF,COX-2,NF-κB in tumor tissue were measured by immunohistochemistry. Results： The tumorigenesis rates of group A,B,C were 100%,100% and 77. 8%,respectively;mainly were high-grade intraepithelial neoplasia. The tumor load in group A was significantly higher than that in group B（ P〈0. 01）,and the spleen index in group B was significantly higher than that in group C（ P〈0. 01）. Serum level of TNF-α was significantly lower（ P〈0. 05） and IL-10 was significantly higher（ P〈0. 05） in group A than that in group B.No significant differences in expressions of VEGF,COX-2,NF-κB were found among group A,B and C. Conclusions： Fp had no obvious effect on the occurrence rate of CAC,and Fp supernatant could decrease the incidence of CAC in mice. Fp and its supernatant could reduce the tumor load via regulating the expressions of TNF-α,IL-10.