碳量子点酒对幽门螺旋杆菌药效学研究及作用机制预测

Pharmacodynamic Study of Carbon Quantum Dot on Helicobacter pylori and Prediction of Its Mechanism

目的:探讨碳量子点女士酒(简称女士酒)、碳量子点碱性白酒(简称碱性酒)对幽门螺杆菌(Helicobacter pylori,Hp)的体内抑菌效果,并结合网络药理学技术预测其作用机制。方法:本研究将70只KM小鼠随机分为空白对照组、模型组、阳性药组、女士酒高、低剂量组以及碱性酒高、低剂量组。除空白对照组外,其余组小鼠灌服菌悬液,构建幽门螺杆菌感染模型。以小鼠体重等一般体征变化、胃部大体形态变化、尿素酶强度以及病理学切片为评价指标,评价其抑制Hp效果。运用网络药理学技术,通过文献筛选酒中健康成分并在TCMSP平台寻找其作用靶点,通过GeneCards数据库采集Hp疾病靶点,将二者交集靶点导入Cytoscape3.7.1软件构建蛋白相互作用(protein-protein interaction,PPI)网络图和“酒-成分-靶点”网络图,之后进行GO和KEGG富集分析。结果:阳性对照组、女士酒高、低剂量组及碱性酒高剂量组与模型组比较,Hp强阳性率、总阳性率均显著降低(P<0.05),并能显著降低尿素酶检测阳性率(P<0.05),减少细菌定植,减轻炎症情况,且疗效呈现剂量依赖性;与模型组比较,女士酒、碱性酒低剂量组炎性细胞明显减少,炎症程度明显降低;女士酒、碱性酒高剂量组几乎不可见炎症反应,胃腺细胞分布较清晰工整。筛选出21个酒中微量健康成分,对应315个作用靶点,检索到905个疾病相关靶点,交集靶点74个。最终分析得到CUL4B、ACTB、PARP1等53个核心靶点,涉及对细菌来源分子的反应、防御反应的调节、溶酶体、氧化还原酶活性等多种生理过程,主要调控IL-17信号通路、TNF信号通路、MAPK信号通路及PI3K-Akt信号通路等。结论:碳量子点酒对Hp具有较好的抑制作用,且酒中微量成分通过多通路作用于多靶点以发挥抑菌作用,为酒可抑制Hp作用提供理论支撑。

Objective:To investigate the in vivo inhibitory effects of carbon quantum dot lady wine(lady wine for short)and carbon quantum dot alkaline liquor(alkaline wine for short)on Helicobacter pylori in mice,and speculation of the mechanism of action of wine by network pharmacology.Methods:70 KM mice were randomly divided into blank control group,model group,positive drug group,high-dose and low-dose group of lady wine,and high and low-dose alkaline alcohol group.Except blank control group,mouse in other groups were gavaged with bacterial suspension to establish Helicobacter pylori infection model.The changes in general physical signs such as body weight,the general morphological changes of mouse stomach,urease intensity and pathological sections were used as evaluation indicators to evaluate the effect of inhibiting Hp.Using network pharmacological analysis to screen the beneficial ingredients in wine through literature,and find its targets on the TCMSP platform,collect Hp disease targets through GeneCards database,take the intersection of the two,and combine the targets Point import uses Cytoscape 3.7.1 software to construct a protein-protein interaction(PPI)network diagram and the“wine-component-target”network diagram,and then perform GO and KEGG enrichment analysis.Results:Compared with the model group,the strong positive rate and total positive rate of Hp in positive control group,lady wine high-dose and low-dose groups and alkaline wine high-dose groups were significantly decreased(P<0.05),it could ignificantly reduce the positive rate of urease detection(P<0.05),bacterial colonization and reduce inflammation,and the efficacy was dose-dependent.Compared with the model group,the inflammatory cells and inflammation degree were significantly reduced in lady wine and alkaline wine low-dose groups.In the high-dose group,there was almost no inflammatory reaction,and the distribution of gastric gland cells was clear and neat.Screened out 21trace health components in wine,corresponding to 315 targets,905 disease-related targets and 74 intersection targets were retrieved.Finally,53 core targets such as CUL4B,ACTB,PARP1,etc.were obtained,involving various physiological processes such as the response to bacteria-derived molecules,regulation of defense responses,lysosomes,and oxidoreductase activity,and mainly regulate IL-17 signaling pathway,TNF signaling pathway,MAPK signaling pathway and PI3K-Akt signaling pathway,etc.Conclusion:Carbon quantum dot wine had a good inhibitory effect on Hp,and the trace components in the wine acted on multiple targets through multiple pathways to exert antibacterial effect,providing theoretical support for the inhibitory effect of wine on Hp.