摘要
目的 观察不同剂量蜥蜴胃康方对胃癌肝转移裸鼠肠道菌群的影响。方法 60只裸鼠随机分为正常对照组(10只)和造模组(50只),造模组用HGC-27胃癌细胞通过脾脏注射制备胃癌肝转移模型,造模4周时,随机取正常对照组1只与造模组5只,取裸鼠肝组织通过病理切片对比验证造模是否成功。随后剩余造模组45只裸鼠随机分为模型组、5-氟尿嘧啶(5-FU)组以及蜥蜴胃康方高(2.6 g/mL)、中(1.3 g/mL)、低(0.6 g/mL)剂量组,每组9只。取最后一次灌胃2 h后各组裸鼠新鲜粪便进行16S rRNA基因测序。结果 16S rRNA测序结果显示,与正常对照组相比模型组裸鼠肠道菌群在门水平表现为拟杆菌门、厚壁菌门丰度下降,放线菌门、蓝藻菌门丰度富集。属水平表现为Muribaculaceae丰度显著降低(t=3.514 4,P=0.024 6),拟普雷沃菌属丰度显著富集(t=-4.660 1,P=0.009 6),副拟杆菌属丰度显著富集(t=-4.284 7,P=0.012 8),瘤胃球菌属丰度显著降低(t=3.342 7,P=0.028 8)。经蜥蜴胃康方干预后,胃癌肝转移裸鼠的肠道菌群结构得到了改善,门水平表现为厚壁菌门丰度增加,放线菌门丰度降低,各组间差异有统计学意义(H=11.619 9,P=0.040 4);蓝藻菌门丰度降低,组间差异有统计学意义(H=11.433 1,P=0.043 4)。属水平表现为Muribaculaceae丰度升高,拟普雷沃菌属、副拟杆菌属丰度降低;瘤胃球菌属(H=14.658 4,P=0.011 9)、乳杆菌属(H=11.386 0,P=0.044 2)丰度显著富集,各组间差异有统计学意义(P<0.05)。结论 蜥蜴胃康方能增加厚壁菌门丰度,降低放线菌门、蓝藻菌门丰度,提高益生菌乳杆菌属、瘤胃球菌属丰度,降低致病菌肠杆菌属、梭状芽胞杆菌属丰度。其中以蜥蜴胃康方高剂量组对肠杆菌属、梭状芽胞杆菌属的抑制作用最显著,并能有效提高乳杆菌属丰度,从而调节胃癌肝转移裸鼠肠道菌群的平衡,增强肠黏膜免疫屏障,激活免疫细胞释放肿瘤坏死因子来发挥对胃癌的抑制作用。
Objective To observe the effect of different doses of Lizards Weikang Formula(LWF) on gut microbiota in nude mice with gastric cancer liver metastasis(GCLM). Methods A total of 60 nude mice were randomly divided into normal control group(n=10) or model group(n=50). The model group was injected with HGC-27 gastric cancer cells into the spleen to create GCLM model. After 4 weeks when successful modeling was confirmed with pathological sections, the model mice were randomly divided into model group, 5-fluorouracil(5-FU) group, and LWF high-, medium-and low-dose groups(2.6 g/mL,1.3 g/mL, 0.6 g/mL), with 9 nude mice in each group. Fresh feces of nude mice in each group were sequenced for 16 S rRNA gene 2 hours after the last intragastric administration. Results Compared with the normal control group, the abundances of Bacteroidetes and Firmicutes in the gut of nude mice in model group decreased, and Actinobacteriota and Cyanobacteria significantly enriched(all P<0.05). At the genus level, the abundances of Muribaculaceae and Ruminococcus significantly decreased(all P<0.05), while those of Alloprevotella and Parabacteroides significantly enriched(all P<0.05). After LWF intervention, the gut microbiota structure of nude mice with GCLM was improved;the abundance of Firmicutes increased at phylum level, while those of Actinobacteriota and Cyanobacteria decreased, with significant differences among groups(all P<0.05). At the genus level, the abundances of Muribaculaceae increased, those of Alloprevotella and Parabacteroides decreased, while Ruminococcus and Lactobacillus significantly enriched, with significant difference among groups(all P<0.05). Conclusion Lizards Weikang Formula may decrease the abundance of Actinobacteriota and Cyanobacteria by increasing the abundance of Firmicutes, and increase the abundance of probiotics Lactobacillus and Ruminococcus by decreasing the abundance of pathogenic bacteria Enterobacter and Clostridium. High-dose Lizards Weikang Formula has the most significant inhibition on Enterobacter and Clostridium, and can effectively improve the abundance of Lactobacillus, thus regulating the balance of intestinal flora in nude mice with gastric cancer liver metastasis, enhancing the intestinal mucosal immune barrier to play an inhibitory effect on gastric cancer.
作者
白星
景燕燕
程翻娥
李卫强
BAI Xing;JING Yan-yan;CHENG Fan-e;LI Wei-qiang(Department of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan,Ningxia 750004,China;不详)
出处
《中国微生态学杂志》
CAS
CSCD
2022年第8期877-884,共8页
Chinese Journal of Microecology
基金
国家自然科学基金(81860807)。
关键词
蜥蜴胃康方
胃癌肝转移
肠道菌群
16S
rRNA
高通量测序
Lizards Weikang Formula
Gastric cancer with liver metastasis
Gut microbiota
16S rRNA
High-throughput sequencing
