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1.新疆医科大学 中医学院,乌鲁木齐 830011
2.新疆维吾尔自治区 中西医结合医院,乌鲁木齐 830000
Received:24 December 2024,
Accepted:14 March 2025,
Published Online:19 March 2025,
Published:20 July 2025
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邵昌明,王宏宇,谢姗珊等.治疗慢性萎缩性胃炎新方的挖掘及其对胃阴亏虚证型的验证[J].中国实验方剂学杂志,2025,31(14):105-113.
SHAO Changming,WANG Hongyu,XIE Shanshan,et al.Excavation of New Prescription for Chronic Atrophic Gastritis and Its Verification of Syndrome Type of Deficiency of Stomach Yin[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(14):105-113.
邵昌明,王宏宇,谢姗珊等.治疗慢性萎缩性胃炎新方的挖掘及其对胃阴亏虚证型的验证[J].中国实验方剂学杂志,2025,31(14):105-113. DOI: 10.13422/j.cnki.syfjx.20250412.
SHAO Changming,WANG Hongyu,XIE Shanshan,et al.Excavation of New Prescription for Chronic Atrophic Gastritis and Its Verification of Syndrome Type of Deficiency of Stomach Yin[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(14):105-113. DOI: 10.13422/j.cnki.syfjx.20250412.
目的
2
筛选及评估用于治疗慢性萎缩性胃炎(CAG)的中药新方及用药剂量,通过网络药理学筛选出中药新方治疗CAG的活性成分与靶点,构建中药新方与疾病之间的关系,探究中药新方治疗CAG的作用机制。
方法
2
检索中国期刊全文数据库(CNKI)、维普、万方数据库,搜索相关中医复方治疗CAG的文献,并应用中医传承辅助平台V3.0建立数据库得出核心药物的组合及中药新方,采用德尔菲调查问卷的方式用于评估中药新方。通过网络药理学研究基于中药系统药理学数据库与分析平台(TCMSP)、HERB数据库检索中药新方的有效成分,使用在线人类孟德尔遗传数据库(OMIM)、GeneCard及DisGeNET数据库检索CAG的有效靶点;利用Venny数据库筛选出中药新方与CAG的共同靶点,基于STRING数据库进行蛋白互作(PPI)网络,筛选出核心靶点使用DAVID数据库进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析,预测出中药新方治疗CAG的有效成分及潜在的靶点及信号通路。实验研究将雄性55只SD大鼠分为空白组及造模组,造模组采用多因素法造模,造模成功后将造模组随机分为模型组、中药新方组、养胃舒组各12只,连续灌胃56 d。解剖取材后使用苏木素-伊红(HE)染色检测大鼠胃黏膜的病理情况;酶联免疫吸附测定法(ELISA)检测大鼠血清中的白细胞介素-1
β
(IL-1
β
)、白细胞介素-6(IL-6)、肿瘤坏死因子-
α
(TNF-
α
)、胃泌素17(G-17)水平的表达;蛋白免疫印迹法(Western blot)检测大鼠胃组织丝裂原活化蛋白激酶(MAPK)、细胞外调节蛋白激酶(ERK)、核因子E
2
相关因子2(Nrf2)蛋白的表达水平。
结果
2
通过数据挖掘及德尔菲调查问卷评估中药新方的组成由莪术15 g、白芍15 g、当归15 g、枸杞子10 g、川楝子15 g、粳米15 g共6味药组成。通过网络药理学分析,中药新方的主要成分为
β
-谷甾醇、亚油酸乙酯、槲皮素、植物甾醇(豆甾醇)、胆固醇5种共有成分,分析出中药新方与CAG共有靶点94个,其中以转化生长因子-
β
1
(TGF-
β
1
)、低聚果糖(FOS)、TNF、IL-1
α
、IL-1
β
、胱天蛋白酶-3(Caspase-3)、蛋白激酶B1(Akt1)、TP53等为核心靶点;GO分析共筛选出401个条目,KEGG富集分析出以MAPK信号通路等133个条目。动物实验结果表明,通过HE染色表明中药新方组及养胃舒组对于腺体萎缩及肠化有一定的改善;ELISA结果表明,与模型组比较,中药新方组及养胃舒组血清中IL-1
β
、IL-6、TNF-
α
的表达水平均下降(
P
<
0.05,
P
<
0.01)、G-17的表达水平均提高(
P
<
0.01);Western blot结果表明,与模型组比较,胃组织中MAPK、ERK蛋白的表达水平均下降(
P
<
0.01);Nrf2蛋白的表达水平升高(
P
<
0.01)。
结论
2
通过数据挖掘筛选出中药新方组有效改善大鼠胃黏膜的萎缩情况,主要与调控炎症反应及氧化应激反应密切相关,可能与网络药理学预测的MAPK/ERK/Nrf2信号通路相关。
Objective
2
To screen and evaluate the new prescription and dosage of traditional Chinese medicine for the treatment of chronic atrophic gastritis (CAG), to screen out the active components and targets of the new prescription of traditional Chinese medicine for the treatment of CAG through network pharmacology, to construct the relationship between the new prescription of traditional Chinese medicine and the disease, and to explore the mechanism of the new prescription of traditional Chinese medicine for the treatment of CAG.
Methods
2
China National Knowledge Infrastructure(CNKI), VIP and Wanfang databases were searched to search for relevant literature on CAG treated by traditional Chinese medicine compound prescriptions. The database was established by using the traditional Chinese medicine inheritance support platform V3.0 to obtain the combination of core drugs and new prescriptions of traditional Chinese medicine. The Delphi questionnaire was used to evaluate the new prescriptions of traditional Chinese medicine.Through network pharmacology research, the effective components of new prescriptions of traditional Chinese medicine were searched based on Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and HERB databases, and the effective targets of CAG were searched using nline Mendelian Inheritance in Man(OMIM), GeneCard and DisGeNET databases. Venny database was used to screen out the common targets of new Chinese medicine and CAG.Protein-protein interaction (PPI) network was carried out based on STRING database. DAVID database was used to screen out the core targets for GO and KEGG enrichment analysis, and the effective components, potential targets and signaling pathways of new Chinese medicine in the treatment of CAG were predicted. In the experimental study, 55 male SD rats were divided into blank group and model group. The model group was modeled by
multi-factor method. After successful modeling, the model group was randomly divided into model group, new Chinese medicine group and Yangweishu group, with 12 rats in each group. Continuous gavage for 56 days. After anatomical sampling, hematoxylin-eosin (HE) staining was used to detect the pathological conditions of gastric mucosa in rats. The levels of interleukin-1
β
( IL-1
β
), interleukin-6 (IL-6), tumor necrosis factor-
α
(TNF-
α
) and gastrin-17 (G-17) in serum of rats were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase(MAPK), extracellular regulated protein kinases(ERK) and nuclear factor E
2
-related factor 2 (Nrf2) protein in gastric tissue of rats were detected by Western blot.
Results
2
Through data mining and Delphi questionnaire evaluation, the composition of the new prescription of traditional Chinese medicine was composed of Curcumae Rhizoma 15 g, Paeoniae Radix Alba 15 g, Angelicae Sinensis Radix 15 g, Lycii Fructus 10 g, Toosendan Fructus 15 g and japonica rice 15 g. Through network pharmacology analysis, the main components of the new prescription of traditional Chinese medicine are
β
-sitosterol, ethyl linoleate, quercetin, phytosterol (stigmasterol ) and cholesterol. Five common components, 94 common targets between the new prescription of traditional Chinese medicine and CAG were analyzed, of which transforming growth factor-
β
1
(TGF-
β
1
), Fructooligosaccharides(FOS), TNF, IL-1
α
, IL-1
β
, Caspase-3, protein kinase B1(Akt1), TP53 were the core targets , a total of 401 items were screened out by GO analysis, and 133 items such as MAPK signaling pathway were analyzed by KEGG enrichment.The results of animal experiments showed that HE staining showed that the new Chinese medicine group and Yangweishu group had certain improvement
in gland atrophy and intestinal metaplasia. ELISA results showed that compared with the model group, the expression levels of IL-1
β
, IL-6 and TNF-α in the serum of the new Chinese medicine group and Yangweishu group decreased (
P
<
0.05,
P
<
0.01 ), and the expression level of G-17 increased (
P
<
0.01 ). Western blot results showed that compared with the model group, the expression levels of MAPK and ERK proteins in gastric tissue decreased (
P
<
0.01). The expression level of Nrf2 protein was increased (
P
<
0.01).
Conclusion
2
Through data mining, it is screened that the new Chinese medicine group can effectively improve the atrophy of gastric mucosa in rats, which is mainly closely related to the regulation of inflammatory response and oxidative stress response, and may be related to the MAPK/ERK/Nrf2 signaling pathway predicted by network pharmacology.
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