文献类型：期刊文献

中文题名：基于网络药理学探讨黄芪建中汤对胃溃疡的保护作用及机制研究

英文题名：Study of the Protective Effect and Mechanism of Huangqi Jianzhong Decoction on Gastric Ulcer Based on Network Pharmacology

作者：白敏[1,2];段永强[1,2];杨晓轶[1,2];王强[1,2];李钦[3];巩子汉[1,2];马骏[1,2]

第一作者：白敏

机构：[1]甘肃中医药大学,兰州730000;[2]敦煌医学与转化教育部重点实验室,兰州730000;[3]甘肃卫生职业学院,兰州730000

第一机构：甘肃中医药大学

年份：2020

卷号：36

期号：4

起止页码：75

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：甘肃省教育厅高等学校科研基金资助项目(编号:2018A-044);甘肃中医药大学科创基金资助项目(编号:KCYB2018-1)。

语种：中文

中文关键词：黄芪建中汤;胃溃疡;网络药理学;实验验证;白介素-6;蛋白激酶;半胱氨酸

外文关键词：Huangqi Jianzhong Decoction;Gastric Ulcer;Network Pharmacology;Experimental Verification;IL-6;AKT;Caspase-3

摘要：目的:基于网络药理学预测和动物模型验证的方法,探讨黄芪建中汤对胃溃疡的保护作用及机制研究。方法:基于网络药理学预测得到黄芪建中汤治疗胃溃疡的可能作用靶点和通路,采用综合造模法(苦寒泻下法+改良obake法+饥饱失常法)复制脾胃虚寒型胃溃疡大鼠模型,黄芪建中汤水煎液灌胃干预,持续治疗21 d。观察大鼠一般生存状况、胃组织病理改变,同时采用蛋白免疫印迹法(WB)以及实时荧光定量PCR法(RT-PCR)对预测结果中相关度最高的三个靶点进行基因以及蛋白含量的测定。结果:预测黄芪建中汤主要活性成分36种,"黄芪建中汤-胃溃疡"共享靶点59个。GO生物功能注释表明共享靶点主要富集于蛋白磷酸酶结合、泛素样蛋白连接酶结合、激活转录因子结合等20个关键生物过程,而KEGG富集分析表明共享靶点与Endocrine resistance、MAPK signaling pathway、HIF-1 signaling pathway、ErbB signaling pathway等8条信号通路密切相关。动物模型验证结果:与空白对照组比较,模型对照组大鼠一般生存状况相对较差,胃组织白介素-6(IL-6)、蛋白激酶B(AKT)、半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)基因蛋白表达水平明显上调(P<0.05);与模型对照组比较,黄芪建中汤能够显著改善大鼠一般生存状况,促进溃疡周围组织的再上皮化,进而迁移覆盖溃疡部位,不同程度降低胃组织中IL-6、AKT、Caspase-3基因、蛋白表达水平,其中尤以黄芪建中汤16 g/kg组明显(P<0.05)。结论:黄芪建中汤对于脾胃虚寒型胃溃疡模型大鼠胃损伤具有显著保护作用体现了中药多成分-多靶点-多途径的特点,其促进胃黏膜修复的具体机制可能与降低炎性因子表达、平衡氧化/抗氧化反应、抑制细胞凋亡等多个因素有关。
Objective:Based on network pharmacology prediction and animal model validation, the protective effect and mechanism of Huangqi Jianzhong Decoction on gastric ulcer were studied.Methods:Based on the prediction of network pharmacology, the possible targets and pathways of Huangqi Jianzhong decoction in the treatment of gastric ulcer were obtained. Then,gastric ulcer rat model with Piweixuhan type was established by the comprehensive modeling method(Kuhanxiexia method + improved obake method + Jibaoshichang method). Huangqi jianzhong decoction was administered for 21 days. The general survival status and pathological changes of gastric tissue were observed. The genes and protein contents of the three targets with the highest correlation in the prediction results were determined by Western blotting(WB) and real-time fluorescence quantitative PCR(RT-PCR).Results:36 main active components of Huangqi Jianzhong Decoction were predicted, and 59 shared targets of "Huangqi Jianzhong decoction gastric ulcer" were predicted. Go biological function annotation showed that the shared targets were mainly enriched in 20 key biological processes, such as protein phosphatase binding, ubiquitin like protein ligase binding, activating transcription factor binding. KEGG enrichment analysis showed that the shared targets were closely related to eight signal pathways, such as endocrine resistance, MAPK signaling pathway, HIF-1 signaling pathway and ERBB signaling pathway. Animal model validation results showed: Compared with the control group, the general survival condition of rats in the model group was relatively poor,and the protein expression levels of IL-6, AKT, Caspase-3 gene in gastric tissues were significantly increased(P<0.05). Compared with the model group, the drug significantly improved the general survival status of rats, promoted the re epithelization of the tissue around the ulcer, and then migrated to cover the ulcer site, and reduced the expression levels of IL-6, AKT, Caspase-3 gene protein in the gastric tissue to varying degrees,while the results in 16 g/kg Huangqi Jianzhong Decoction group showed the significant difference(P<0.05).Conclusion: Huangqi Jianzhong decoction has a significant protective effect on gastric injury in gastric ulcer rats with Piweixuhan syndrome, which suggests its traditional Chinese characteristics of multi-component, multi-target and multi-channel. The specific mechanism of promoting gastric mucosa repair may be related to reducing the expressions of inflammatory factors, balancing oxidation/anti-oxidation reaction and inhibiting apoptosis, etc.