结直肠癌小鼠肠道菌群变化及其对血清CD40L、炎症因子水平的影响

Changes of intestinal flora,serum CD40L and inflammatory factors in colorectal cancer rat

目的探究结直肠癌(CRC)大鼠肠道菌群变化与肿瘤发生发展的相关性及对血清可溶性CD40配体(sCD40L)和炎症因子水平的影响。方法选取30只Wistar大鼠注射40 mg/kg 1,2-二甲基肼(DMH)建立结直肠肿瘤诱导模型,另选取30只非肿瘤诱导大鼠作为对照组。两组均给予相同饮食,获取大鼠肠道粪便样本,采用菌落培养比较两组肠道菌群结构差异,并分析与结直肠癌发生的相关性。采用ELISA检测两组血清sCD40L、肠腔冲洗液白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)水平。结果DMH注射1周后,建模组与对照组大鼠脾重、体重、肠道菌群菌结构比较差异无统计学意义(P>0.05)。DMH注射7周和11周后,建模组肠道群落结构与对照组比较差异有统计学意义(P<0.05);建模组异变腺窝病灶(ACF)显著高于对照组,两组比较差异有统计学意义(P<0.05)。菌落培养结构显示,建模组相对于对照组梭杆菌门、拟杆菌门落数显著升高,放线菌门、厚壁菌门、变形菌门菌落数显著降低,两组比较差异均有统计学意义(P<0.05)。DMH注射时、注射1周后两组大鼠血清sCD40L、肠腔冲洗液IL-2、IL-6、IFN-γ及TNF-α水平比较差异无统计学意义(P>0.05);DMH注射7周和11周后,建模组相较于对照组血清sCD40L、肠腔冲洗液IL-2、IL-6、IFN-γ及TNF-α水平显著升高,两组比较差异有统计学意义(P<0.05)。结论结直肠癌诱导大鼠模型随着结直肠癌的发生发展肠道菌群发生明显变化,并导致机体局部sCD40L和炎症因子水平异常。

Objective To investigate the relationship between the changes of intestinal flora,serum soluble CD40 ligand(sCD40L)and inflammatory factors and tumorigenesis in colorectal cancer(CRC)rats.Methods Thirty Wistar rats were injected with 40 mg/kg of 1,2-dimethylhydrazine(DMH)to establish a tumor-inducing model.Another 30 non-tumorinducing rats were selected as the control group.Colonic fecal samples were compared by colony culture.The differences in intestinal flora between the two groups were analyzed and analyzed for correlation with colorectal cancer.ELISA was used to detect serum sCD40L,intestinal lavage fluid interleukin-2(IL-2),interleukin-6(IL-6),gamma interferon(IFN-γ),and tumor necrosis factor alpha(TNF-α)levels.Results After 1 week of DMH injection,there was no significant difference in spleen weight,body weight and intestinal flora between the model group and the control group(P>0.05).After 7 and 11 weeks of DMH injection,the intestinal community structure of the model group was significantly different from that of the control group(P<0.05).The model group had significantly more normal follicular lesions(ACF)than that of the control group(P<0.05).The colony culture showed that the number of gates of the model group was significantly higher than that of the control group,and the number of colonies of actinomycetes,posterior wall bacteria and proteobacteria were significantly decreased(P<0.05).There was no significant difference in serum sCD40 L,intestinal lavage fluid IL-2,IL-6,IFN-γand TNF-αbefore and after 1 week of DMH injection(P>0.05).After 7 and 11 weeks of DMH injection,serum sCD40 L,intestinal lavage fluid IL-2,IL-6,IFN-γand TNF-αlevels were significantly higher in the model group than those in the control group(P<0.05).Conclusion There were significant changes of sCD40L and inflammatory factors levels in the colorectal cancer-induced rat model,and might be correlated with the development of colorectal cancer.