摘要
目的探讨丁酸钠(NaB)对氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的炎症相关性结直肠癌小鼠模型及其肠道菌群的影响。方法将40只6周龄C57BL/6J小鼠通过随机数字法分为对照组(Control)、造模组(Model)、低剂量(1.90 g/L)NaB干预造模组(L-NaB)和高剂量(2.85 g/L)NaB干预造模组(H-NaB)。Model、L-NaB和H-NaB组一次性腹腔注射AOM 10 mg/kg,饮用3%DSS水溶液5 d,自由饮水16 d为1个周期,循环3个周期。Model组自由饮水期间,L-NaB和H-NaB组分别饮用不同浓度的NaB水溶液;112 d实验结束。收集小鼠粪便进行DNA提取及高通量菌群测序,收集小鼠结直肠并观察其长度和出血情况,记录肿瘤大小和数目,并对结直肠进行Ki-67染色。结果Control、Model、L-NaB和H-NaB组小鼠结直肠长度分别为(7.53±0.95)、(6.39±0.94)、(7.08±0.61)和(7.45±0.77)cm,F=3.227,P=0.037。与Control组相比,Model组小鼠结直肠长度下降,P=0.008;与Model组相比,H-NaB组小鼠结直肠长度增加,P=0.025。Model、L-NaB和H-NaB组肿瘤体积分别为(7.44±7.00)、3.29和(2.07±0.68)mm;。Ki-67染色结果表明,AOM/DSS促进结直肠组织增殖,NaB干预可以抑制结直肠组织增殖;Model组小鼠α多样性有下降趋势,NaB干预可一定程度恢复α多样性。主成分分析(PCA)结果表明,Model与Control组菌群组成相差最多,NaB干预与Control组接近。线性判别分析(LEfSe)结果显示,Control组显著差异物种为f;uribaculaceae和s;cateroides;ulgatus,L-NaB组为g;ordonibacter、g;achnoclostridium,H-NaB组为g;doribacter。在门水平,H-NaB改善AOM/DSS干预造成的拟杆菌门丰度降低,P=0.046;在属水平,H-NaB拟普雷沃菌属丰度相对Model组上调,P=0.007;并且AOM/DSS上调帕拉普氏菌属丰度,P=0.001;与Model组比,L-NaB和H-NaB降低帕拉普氏菌属丰度,P值分别为0.001和0.004。结论在AOM/DSS诱导的炎症相关性结直肠癌小鼠模型中,NaB可改善AOM/DSS引起的肠道炎症,对结直肠细胞增殖有一定抑制作用,并影�
Objective To explore the effect of sodium butyrate(NaB)on AOM/DSS-induced inflammation associated colorectal cancer model in mice and its influence on the gut microbiota.Methods Forty 6-week-old C57 BL/6 J mice were randomly divided into control group(Control),model group(Model),low-dose(1.90 g/L)NaB intervention group(L-NaB)and high-dose(2.85 g/L)NaB intervention group(H-NaB).Mice in model,L-NaB and H-NaB groups were intraperitoneally injected with AOM 10 mg/kg once.Drinking 3%DSS water solution for 5 days and water freely for 16 days were considered as a cycle,which conducted three cycles.During the free drinking period of the Model,the L-NaB and H-NaB groups were given different concentrations of NaB solution.The experiment ended at 112 days,and mouse feces were collected for DNA extraction and high-throughput sequencing.The tumor size and number were recorded,and the colon and rectum were stained with Ki-67 immunohistochemistry.Results The colorectal lengths of Control,Model,L-NaB and H-NaB groups were(7.53±0.95)cm,(6.39±0.94)cm,(7.08±0.61)cm and(7.45±0.77)cm(F=3.227,P=0.037),respectively.Compared with Control group,the colorectal length of Model group was significantly decreased(P=0.008),and that of H-NaB group was significantly increased compared with the Model(P=0.025).The tumor volumes of Model,L-NaB and H-NaB groups were(7.44±7.00),3.29 and(2.07±0.68)mm3,respectively.Ki-67 immunohistochemical results showed that AOM/DSS promoted colorectal tissue proliferation,and NaB intervention could inhibit colorectal tissue proliferation.Theαdiversity of Model group was decreased compared to the Control group,and NaB intervention could restoreαdiversity to a certain extent.PCA results showed that there was the most difference in bacterial composition between Model group and Control group,and NaB intervention groups were close to Control group.LDA Effect Size(LEfSe)analysis showed that the biomarkers in Control group were f_Muribaculaceae and s_Bcateroides_vulgatus,the biomarkers in L-NaB group were G_Gordoni
作者
刘华缓
曹誉
肖志鹏
毛联智
孙素霞
LIU Hua-huan;CAO Yu;XIAO Zhi-peng;MAO Lian-zhi;SUN Su-xia(Department of Nutrition and Food Hygiene,School of Public Health,Southern Medical University,Guangzhou510515,China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2021年第18期1368-1377,共10页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81773429)
国家级大学生创新创业训练计划项目(202012121003)
关键词
丁酸钠
炎症相关性结直肠癌
肠道菌群
短链脂肪酸
AOM/DSS
dietary fiber
sodium butyrate
inflammation associated colorectal cancer
gut microbiota
short-chain fatty acids
AOM/DSS
