文献类型：期刊文献

中文题名：基于网络药理学和动物实验探讨慈菇消脂方对非酒精性脂肪性肝炎“炎癌”转化中EGFR/PI3K/AKT信号通路的干预研究

英文题名：Effect of Cigu Xiaozhi decoction on EGFR/PI3K/AKT signaling pathway in NASH's“inflammatory cancer”transformation based on network pharmacology and animal experiments

作者：郑兰兰[1];王莉[1];郭才[1];何燕芳[1];谢娇娇[1];马燕花[1]

第一作者：郑兰兰

机构：[1]甘肃中医药大学第一临床医学院,甘肃兰州730000

第一机构：甘肃中医药大学临床医学院

年份：2024

卷号：40

期号：8

起止页码：1573

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：CSTPCD;;Scopus;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金地区基金项目(No.81860821);联合科研基金一般项目(No.23JRRA1523)。

语种：中文

中文关键词：网络药理学;慈菇消脂方;NASH;炎癌;EGFR;PI3K/AKT信号通路

外文关键词：network pharmacology;Cigu Xiaozhi decoction;NASH;inflammatory cancer;EGFR;PI3K/AKT signaling pathway

摘要：目的基于网络药理学研究慈菇消脂方(Cigu Xiaozhi decoction,CXD)的主要活性成分、关键靶点及通路,分析其对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)“炎癌”转化的作用机制,并进行动物实验验证。方法基于网络药理学预测得到CXD治疗NASH“炎癌”转化的潜在作用靶点和信号通路。采用蛋氨酸-胆碱缺乏饮食(MCD)诱导小鼠NASH模型,给予CXD及表皮生长因子受体(EGFR)抑制剂干预28 d,干预结束后处死小鼠,苏木精-伊红法(HE)观察各组小鼠肝脏组织形态学变化;Western blot检测各组小鼠肝组织EGFR、磷脂酰肌醇3-激酶(PI3K)及蛋白激酶B(AKT)蛋白相对表达量;酶联免疫吸附测定法(ELISA)检测各组小鼠血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的含量;结果经网络药理学筛选得到CXD潜在活性成分284个、潜在治疗靶点159个及关键靶点20个。CXD可影响细胞增殖、炎症反应等多个生物过程,涉及肿瘤、PI3K/AKT等多个信号通路。动物实验验证结果表明CXD能够降低NASH小鼠血清中IL-6、IL-1β、TNF-α的水平;降低肝组织中PI3K、AKT蛋白相对表达量,升高EGFR蛋白的相对表达量。结论CXD可通过参与细胞增殖和炎症反应等生物过程,调控EGFR/PI3K/AKT信号通路,改善NASH小鼠的肝组织损伤。
Aim To study the main active ingredients,key targets and pathways of Cigu Xiaozhi Decoction(CXD)based on network pharmacology,and to analyze and verify the mechanism of CXD on the transformation of“inflammatory cancer”in non-alcoholic steatohepatitis(NASH)by animal experiments.Methods The potential targets and signaling pathways of CXD in the treatment of NASH“inflammatory carcinoma”were predicted based on network pharmacology.The mouse model of NASH was induced by methionine-choline deficiency diet(MCD),and CXD and epidermal growth factor receptor(EGFR)inhibitors were given for 28 days.The mice were killed after the intervention,and the liver histopathology of each group was observed by hematoxylin-eosin method(HE).The relative expression levels of EGFR,phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT)in liver tissue of mice in each group were detected by Western blot.The contents of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosorbent assay(ELISA).Results A total of 284 potential active components,159 potential therapeutic targets and 20 key targets of CXD were identified by network pharmacological screening.CXD could affect multiple biological processes such as cell proliferation and inflammatory response,involving multiple signaling pathways such as tumor and PI3K/AKT.Animal experiments showed that CXD could reduce the levels of IL-6,IL-1βand TNF-αin serum of NASH mice.The relative expression of PI3K and AKT protein in liver tissue decreased,and the relative expression of EGFR protein was increased.Conclusion CXD can regulate EGFR/PI3K/AKT signaling pathway by participating in biological processes such as cell proliferation and inflammatory response,and improve liver tissue injury in NASH mice.