首页|基于蛋白质组学揭示马齿苋通过抑制Caspase 12蛋白对结直肠炎癌转化小鼠的药效机制研究

基于蛋白质组学揭示马齿苋通过抑制Caspase 12蛋白对结直肠炎癌转化小鼠的药效机制研究

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目的:探讨马齿苋通过Caspase 12介导的NOD信号通路对结直肠炎癌转化小鼠的保护作用机制。方法:将24只6~8周龄的C57小鼠,随机分为正常对照组、模型组、马齿苋治疗组。模型组和马齿苋治疗组采用氧化偶氮甲烷(AOM)联合葡聚糖硫酸钠(DSS)诱导结直肠炎相关肿瘤发生小鼠模型,马齿苋治疗组每日按照人鼠等效剂量灌胃;通过各组小鼠的脾体比、结直肠长度、肠道息肉/肿瘤总数及肠道组织的苏木精-伊红染色,分析马齿苋抑制小鼠结直肠炎癌转化的药效;通过蛋白组分析、Western blot检测,验证马齿苋对NOD信号通路关键蛋白Caspase 12的调控;分别通过qPCR法和免疫荧光法检测小鼠组织中Caspase 12调控的细胞因子IL-1β、趋化因子和巨噬细胞标志物F4/80的表达;最后采用Alican blue和PAS病理染色检测肠道黏蛋白的水平,使用Western blot检测肠道紧密连接蛋白的水平,以评价马齿苋对肠道屏障的保护作用。结果:马齿苋明显抑制小鼠结直肠炎癌转化进展,减少肠道息肉/肿瘤数量和肠道Ki67水平,马齿苋可显著改善结直肠炎癌转化小鼠NOD样受体信号通路功能,抑制关键蛋白Caspase 12的水平,减少下游细胞因子IL-1β和趋化因子MCP-1含量,减少结直肠炎癌转化小鼠中肠道组织巨噬细胞的表达,改善结直肠炎癌转化小鼠肠道屏障功能。结论:马齿苋能够抑制小鼠结直肠炎癌转化进展,抑制炎症反应,改善肠道屏障,其作用可能与调控Caspase 12介导的NOD样受体信号通路有关。
Mechanistic study of the therapeutic effect of Portulaca oleracea L on colorectal inflammatory cancer transformation in mice by inhibiting Caspase 12 protein based on proteomics
Objective:To investigate the mechanism of the protective effect of Portulaca oleracea L on colorec-tal inflammatory cancer transformation model mice through the NOD signaling pathway mediated by Caspase 12.Methods:Twenty-four C57 mice aged 6-8 W were randomly divided into normal control,model control,and por-tulaca oleracea L treatment groups.In the model control group and portulaca oleracea L treatment group,Azoxy-methane(AOM)combined with Dextran sodium sulfate(DSS)was used to induce colitis-associated tumorigenesis mice model,and in the portulaca oleracea L treatment group,gavage the drug every day according to the equiva-lent dose of human mice.The efficacy of Portulaca oleracea L in inhibiting colorectal cancer transformation mice was analyzed by ratio of spleen/body,colorectal length,total number of polyps/tumors,and HE staining of intes-tinal tissues in each group.Proteomic analysis and Western blot were used to clarify the therapeutic effect of the NOD signaling pathway,especially the key protein Caspase 12.The expression of cytokine IL-1β and macrophage marker F4/80 in mice tissues were detected by qPCR and immunofluorescence,respectively.Finally,the level of intestinal mucin was detected by Alican blue and PAS pathological staining,and the level of intestinal tight junc-tion protein was detected by Western blot,to evaluate the protective effect of Portulaca oleracea L on the intestinal barrier.Results:Portulaca oleracea L significantly inhibited the progression of colorectal inflammatory cancer transformation in mice,and reduced the number of intestinal polyps/tumors and intestinal Ki67 levels.Portulaca oleracea L significantly improved the function of the NOD-like receptor signaling pathway in colorectal inflamma-tory cancer transformation mice,inhibited the level of the key protein Caspase 12,reduced the levels of the down-stream cytokine IL-1β and chemokine MCP-1,and inhibited the expression of macrophages in the intestinal tis-sues.Portulaca oleracea L improved the intestinal barrier function in colorectal inflammation cancer-transformed mice.Conclusion:Portulaca oleracea L significantly inhibited the progression of colorectal inflammatory cancer transformation in mice models,suppressed inflammatory responses,and improved the intestinal barrier,and its effects may be related to the modulation of the Caspase 12-mediated NOD-like receptor signaling pathway.

colorectal inflammatory cancer transformationPortulaca oleracea LCaspase 12intestinal barrier

陆璐、苏杭、季光、徐汉辰

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上海中医药大学附属龙华医院脾胃病研究所(上海,200032)

上海市炎癌转化病证生物学前沿研究基地

结直肠炎癌转化 马齿苋 Caspase 12 肠道屏障

国家自然科学基金国家自然科学基金

8232207682104466

2024

中国中西医结合消化杂志
华中科技大学同济医学院,中国中西医结合学会消化系统疾病专业委员会,中华中医药学会脾胃病专业委员会

中国中西医结合消化杂志

CSTPCD
影响因子:1.363
ISSN:1671-038X
年,卷(期):2024.32(5)