内蒙古医科大学附属医院临床医学研究中心,呼和浩特 010050
Received:11 May 2024,
Revised:2024-09-28,
Accepted:28 October 2024,
Published:28 October 2025
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魏颖,张杰,孙佳鑫,等.基于网络药理学与16S rDNA测序的探究:中药通关藤对结肠炎相关结直肠癌小鼠模型的干预作用及机制研究[J].重庆医科大学学报,2025,50(10):1363-1374.
Wei Ying,Zhang Jie,Sun Jiaxin,et al.Intervention effect and mechanism of Chinese herbal medicine Marsdenia tenacissima on a mouse model of colitis-associated colorectal cancer: a study based on network pharmacology and 16S rDNA sequencing[J].Journal of Chongqing Medical University,2025,50(10):1363-1374.
魏颖,张杰,孙佳鑫,等.基于网络药理学与16S rDNA测序的探究:中药通关藤对结肠炎相关结直肠癌小鼠模型的干预作用及机制研究[J].重庆医科大学学报,2025,50(10):1363-1374. DOI: 10.13406/j.cnki.cyxb.003767.
Wei Ying,Zhang Jie,Sun Jiaxin,et al.Intervention effect and mechanism of Chinese herbal medicine Marsdenia tenacissima on a mouse model of colitis-associated colorectal cancer: a study based on network pharmacology and 16S rDNA sequencing[J].Journal of Chongqing Medical University,2025,50(10):1363-1374. DOI: 10.13406/j.cnki.cyxb.003767.
目的
2
研究中药通关藤对结肠炎相关结直肠癌(colitis-associatedcolon cancer,CAC)的干预及其活性作用机制。
方法
2
运用高分辨质谱结合精确质量数数据库对通关藤化学成分进行鉴定,同时运用网络药理学方法,筛选当其的主要活性成分和治疗结直肠癌(colorectal cancer,CRC)的相关靶点,对其抗CRC作用机制进行研究。同时构建CAC小鼠模型,考察通关藤对CAC小鼠疾病活动指数(disease activity index,DAI)、体质量、结直肠形态以及血清TNF-α、IL-1β水平的影响。利用16S rDNA测序技术,揭示其对小鼠肠道微生物群落多样性的影响。
结果
2
质谱鉴定出通关藤中50个成分,网络药理学匹配得到37个活性成分,检索出与CRC有关靶点313个。共得到958条GO条目和173条KEGG条目,与通关藤相关度较高主要包括炎症、氧化应激、癌症等相关通路。造模后各组小鼠分别出现了腹泻、便血、脱肛、消瘦等表现,各DSS循环后模型组DAI评分均升高,第一、二、三循环后通关藤组能降低造模后小鼠的DAI评分(
P=
0.007、
P<
0.001、
P<
0.001)。同时,与模型组相比,通关藤组小鼠结直肠长度增长,肠体肿胀减轻,上皮细胞结构相对完整,炎性细胞减少,杯状细胞增多,不典型增生减少,TNF-α、IL-6水平降低(
P
<
0.001、
P
=0.002)。通关藤组小鼠的肠道微生物丰富度和多样性下降,通关藤组与模型组相比,Bacteroides的相对丰度降低,Muribaculaceae和Clostridia-UCG-014的相对丰度增加(
P
=0.002、
P
=0.009)。
结论
2
通关藤具有干预CAC小鼠结直肠癌的作用,其作用机制可能与其调节炎癌相关作用通路及改变肠道微生物群多样性有关。
Objective
2
To investigate the intervention effect and active mechanism of traditional Chinese medicine
Marsdenia tenacissima
on colitis-associated colorectal cancer (CAC).
Methods
2
High-resolution mass spectrometry and a precise mass number database were used to identify the chemical components of
Marsdenia tenacissima
,and network pharmacology methods were used to obtain the main active components and targets of
Marsdenia tenacissima
in the treatment of colorectal cancer (CRC) and analyze its mechanism of action against CRC. A mouse model of CAC was established,and then
Marsdenia tenacissima
was analyzed in terms of its effect on disease activity index (DAI),body mass,colorectal morphology,and serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in CAC mice. Furthermore,16S rDNA sequencing technique was used to assess the impact of
Marsdenia tenacissima
on the diversity of intestinal microbiota in mice.
Results
2
A total of 50 components were identified by mass spectrometry,and 37 active components were identified by network pharmacology. Furthermore,313 targets related to CRC were identified. A total of 958 GO terms and 173 KEGG terms were obtained,among which inflammation,oxidative stress,and cancer pathways showed a relatively high degree of association with
Marsdenia tenacissima
. After modeling,the mice in each group h
ad the manifestations such as diarrhea,bloody stool,prolapse of anus,and weight loss,and the model group had a significant increase in DAI score after each DSS cycle,while the
Marsdenia tenacissima
group had a significant reduction in DAI score of the model mice after the first,second,and third cycles(
P
=0.007,
P
<
0.001,and
P
<
0.001). In addition,compared with the model group,the
Marsdenia tenacissima
group had a significant increase in colorectal length,alleviation of intestinal swelling,a relatively intact structure of epithelial cells,a reduction in inflammatory cell infiltration,a significant increase in goblet cells,a reduction in atypical hyperplasia,and significant reductions in the levels of TNF-α and IL-6 in CAC mice(
P
<
0.001 and 0.002). The
Marsdenia tenacissima
group had significant reductions in the abundance and diversity of intestinal microbiota,and compared with the model group,the
Marsdenia tenacissima
group had a significant reduction in the relative abundance of Bacteroides and significant increases in the relative abundances of Muribaculaceae and Clostridia-UCG-014(
P
=0.002 and 0.009).
Conclusion
2
Marsdenia tenacissima
exerts an intervention effect on colorectal cancer in CAC mice,possibly by regulating the pathways associated with inflammation and cancer and altering the diversity of intestinal microbiota.
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