文献类型：期刊文献

中文题名：基于网络药理学-分子对接技术及体内实验探讨化瘀消痞汤干预萎缩性胃炎癌前病变的作用机制

英文题名：To Explore the Mechanism of Huayu Xiaopi Decoction in the Intervention of Precancerous Lesions of Gastric Cancer Based on Network Pharmacology and Molecular Docking Technique and in vivo Experiment

作者：刘自由[1,2];段永强[3];安耀荣[1,2];张延英[1,4];宋冰[1,4];白敏[1,4];袁晓梅[1,5];彭月[1,5];肖孟勇[1,5];李卫强[3]

第一作者：刘自由

机构：[1]甘肃中医药大学基础医学院,兰州730000;[2]甘肃中医药大学甘肃省中药新产品创制工程实验室,兰州730000;[3]宁夏医科大学中医学院,银川750004;[4]甘肃省实验动物行业技术中心,兰州730000;[5]甘肃省中医方药挖掘与创新转化重点实验室,兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2024

卷号：26

期号：4

起止页码：1092

中文期刊名：世界科学技术-中医药现代化

外文期刊名：Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD_E2023_2024】；

基金：国家中医药管理局重点学科建设项目(国中医药人教函[2023]85号):中医脾胃病学,负责人:李卫强,段永强;宁夏自然科学基金委员会一般项目(2023AAC03170):炎癌视角下从IL-6/JAK/STAT3介导炎性损伤途径研究化瘀消痞方干预慢性萎缩性胃炎癌前病变的效应机制,负责人:段永强

语种：中文

中文关键词：化瘀消痞汤;萎缩性胃炎癌前病变;网络药理学;分子对接

外文关键词：Huayu Xiaopi Decoction;Atrophic gastritis precancerous lesion;Network pharmacology;Molecular docking

摘要：目的基于网络药理学和分子对接技术预测化瘀消痞汤干预萎缩性胃炎癌前病变(Precancerous lesions of gastric cancer,PLGC)作用靶点和分子机制,并进行实验验证。方法60只SPF级SD雄性大鼠,随机选取10只为空白对照,其余大鼠进行PLGC模型复制,造模成功后随机分为模型组,叶酸组(2 mg·kg^(-1)·d^(-1)),化瘀消痞汤高、中、低剂量组(24.8、12.4、6.2 g·kg^(-1)·d^(-1)),连续给药干预90天,记录大鼠体质量和3 h进食量,HE染色观察大鼠胃组织病理形态;采用网络药理学和分子对接技术预测化瘀消痞汤干预PLGC的潜在靶点,采取Western blot技术对核心靶点进行验证。结果与空白组比较,模型组大鼠体质量和3 h进食量明显降低(P<0.05),镜下见大鼠胃黏膜明显变薄,腺体明显减少并且排列紊乱,部分区域可见肠上皮化生的杯状细胞及大量炎性细胞浸润,与模型组相比较,各给药组大鼠体质量和3 h进食量不同程度改善,化瘀消痞汤中、高剂量改善明显(P<0.05),大鼠胃黏膜不同程度的修复,腺体排列趋于整齐,间质炎性细胞逐渐减少。网络药理学及分子对接结果表明TP53、JUN、MAPK3/1(ERK1/2)是化瘀消痞汤干预PLGC的核心靶点。分子生物学检测结果显示:与空白组相比较,模型组大鼠胃组织中TP53、c-Jun、ERK1/2蛋白磷酸化水平显著升高(P<0.05);与模型组相比较,各给药组大鼠胃组织中TP53、c-Jun、ERK1/2蛋白磷酸化水平不同程度降低,其中化瘀消痞汤高、中剂量组显著降低(P<0.05)。结论化瘀消痞汤可明显改善PLGC大鼠生存状况,促进胃黏膜修复,其具体机制可能与化瘀消痞汤降低PLGC大鼠胃组织中ERK1/2、c-Jun、TP53蛋白磷酸化水平,进而调节下游信号分子响应有关。
Objective To predict the target and molecular mechanism of Huayu Xiaopi decoction in the intervention of Precancerous lesions of gastric cancer(PLGC)based on network pharmacology and molecular docking technology,and to conduct experimental verification.Methods A total of 60 SPF SD male rats were randomly selected as blank control,and the other rats were replicated in PLGC model.After successful modeling,the rats were randomly divided into model group,folic acid group(2 mg·kg^(-1)·d^(-1)),Huayu Xiaopi decoction high,medium and low dose groups(24.8,12.4,6.2 g·kg^(-1)·d^(-1)),which were continuously administered for 90 days.The body mass and food intake of rats at 3 h were recorded,and the gastric histopathology was observed by HE staining.Network pharmacology and molecular docking techniques were used to predict the potential targets of Huayu Xiaopi decoction in PLGC intervention,and the core targets were verified by Western blot technique.Results Compared with the blank group,the body mass and 3 h food intake of rats in the model group were significantly decreased(P<0.05),the gastric mucosa of rats was significantly thinner,the glands were significantly reduced and disordered,and the intestinal metaplasia goblet cells and a large number of inflammatory cells were visible in some areas.Compared with the model group,the body mass and 3 h food intake of rats in each administration group were improved to varying degrees.Huayu Xiaopi Decoction improved significantly in medium and high doses(P<0.05),the gastric mucosa was repaired in different degrees,the glandular arrangement tended to be orderly,and the inflammatory cells in the interstitial were gradually reduced.The results of network pharmacology and molecular docking showed that TP53,JUN and MAPK3/1(ERK1/2)were the core targets of Huayu Xiaopi decoction in the intervention of PLGC.Molecular biological detection results showed that compared with blank group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of model group were significantly increased(P<0.05).Compared with model group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of rats in all administration groups were decreased to different degrees,and significantly decreased in Huayu Xiaopi decoction high-dose and medium-dose groups(P<0.05).Conclusion Huayu Xiaopi Decoction can significantly improve the survival condition of PLGC rats and promote gastric mucosal repair,the specific mechanism of which may be related to the decrease of ERK1/2,c-Jun and TP53 protein phosphorylation levels in gastric tissue of PLGC rats,and then regulate the downstream signaling molecular response.