Objective:To investigate the potential key targets of Liujun Anwei Prescription and its effects on NF-κB/iNOS-NO in small intestine of mice with chemotherapy- associated diarrhea; To reveal the anti-inflammatory components and molecular mechanism.Methods:UPLC-Q/TOF MS combined with UNIFI software was used to analyze the chemical components of Liujun Anwei Prescription. PubChem database was searched to obtain the active components of Liujun Anwei Prescription, and the Swiss Target Prediction was used to predict the targets. The database of DisGeNET, OMIM and GeneCards were searched to obtain the targets of chemotherapy-related diarrhea. The potential targets of Liujun Anwei Prescription in the treatment of chemotherapy-related diarrhea diseases were obtained by crossing the targets of active components of Liujun Anwei Prescription and those related to diarrhea diseases. The PPI network and component-target-pathway network were constructed by Cytoscape 3.7.1 software, and the intersecting targets were analyzed by GO and KEGG based on David Database. The potential active components and potential targets predicted in the network were verified by using Autodock software. 60 C57BL/6J male mice were divided into normal control group, model group, positive control group and Liujun Anwei Prescription high-, medium- and low-dosage groups according to random number table method, with 10 mice in each group. In addition to the normal control group, the other groups of mice were intraperitoneally injected with 5-fluorouracil injection 50 mg/kg preparation to construct CID mouse model. After 14 days, the expressions of NF-κB and iNOS in jejunum were detected by Western blot.Results:A total of 197 compounds were identified, and 156 key compounds of Liujun Anwei Prescription were screened, involving 82 potential targets, mainly through NOS2 and other key targets, playing a role through cancer pathway, PI3K-Akt, NF-κB signal pathway. The experimental results showed that Liujun Anwei Prescription could significantly down-regulate the protein expressions of NF-κB and iNOS.Conclusion:This study reveals the pharmacodynamic material basis of Liujun Anwei Prescription, which can be achieved by decreaseing the levels of NF-κB and iNOS to affect the inflammatory response of intestinal tissue, improve intestinal mucosal barrier function, and thus improve chemotherapy related diarrhea.

目的 通过网络药理学方法探讨六君安胃方减少结肠癌化疗期间消化道不良反应的作用机制.方法 通过检索中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)对六君安胃方中六味中药的化学成分、作用靶点进行筛选,并在GeneCards、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man,OMIM)等相关数据库中筛选出"chemotherapy-induced nausea and vomiting(CINV)"、"chemotherapy-induced diarrhea(CID)"相关靶点.利用STRING和Cytoscape3.6.0构建PPI网络图并通过网络拓扑分析获得关键蛋白靶点;利用R软件ClusterProfiler进行GO及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路功能富集分析;利用AutoTools1.5.6进行有效化学成分与关键蛋白靶点的分子对接.结果 六君安胃方中的中药有效化学成分共103个,潜在作用靶点406个,CINV、CID疾病相关作用靶点851个,通过PPI网络拓扑分析得到关键蛋白靶点,前5个分别为AKT1、MAPK3、MAPK1、MAPK8、JUN;GO富集结果显示,氧化应激反应、凋亡信号通路调节、膜筏、膜微区域、泛素样蛋白连接酶结合、蛋白质丝氨酸/苏氨酸激活酶活性等排名靠前;KEGG富集通路结果显示,PI3K-AKt信号通路、MAPK信号通路、TNF信号通路等信号通路为主要作用通路;分子对接显示党参中的木犀草素与AKT1结合性最好.结论 六君安胃方可能通过调节AKT1、MAPK3、MAPK1等关键蛋白,干预PI3K-AKt等相关炎症信号通路来减少化疗期间消化道不良反应.

将中医理论与化疗不良反应现代研究相结合,创“两阶段三步曲法”融入到结直肠癌辅助化疗过程中.化疗第1周为健脾和胃阶段,运用六君安胃汤顾护中焦脾胃后天之本,减轻消化道不良反应,即第一步;化疗第2、3周为健脾补肾阶段,运用芪菟二至汤调补先后天之本,防治骨髓抑制,即第二步;另外,运用辛凉解表、清热解毒法治疗化疗期间外感热病,即第三步.通过分阶段辨病辨证治疗可减轻化疗不良反应,提高化疗完成率,从而降低肿瘤复发转移.