中药新药与临床药理2026，Vol.37Issue(4)：644-654,11.DOI:10.19378/j.issn.1003-9783.2026.04.007
基于转录组学探讨半夏泻心汤对大鼠慢性萎缩性胃炎的作用机制
Exploring the Mechanism of Banxia Xiexin Decoction in Ameliorating Chronic Atrophic Gastritis in Rats Based on Transcriptomics
摘要
Abstract
Objective To explore the mechanism of Banxia Xiexin Decoction(BXD)in ameliorating chronic atrophic gastritis(CAG)based on transcriptomics.Methods A CAG rat model was established using a multifactorial combined modeling method over a total period of 24 weeks.Sixty male SD rats were randomly divided into six groups(n=10):a normal control group,a model group,a positive drug group(vitacoenzyme,200 mL·kg⁻¹),low(2.5 g·kg⁻¹),medium-(5.0 g·kg⁻¹),and high-(10.0 g·kg⁻¹)dose BXD groups.After successful modeling,rats in the treatment groups were administered the corresponding drugs via gavage,while rats in the normal and model groups received an equal volume of distilled water for 4 consecutive weeks.General conditions such as body mass were observed.Pathological changes in gastric tissue were evaluated by hematoxylin-eosin(HE)and Alcian blue-periodic acid Schiff(AB-PAS)staining,and pathological scores were assigned.Levels of superoxide dismutase(SOD),malondialdehyde(MDA),myeloperoxidase(MPO),tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-6,and IL-18 in gastric tissue were detected using assay kits.Transcriptomic analysis was performed to screen differentially expressed genes(DEGs)in gastric tissue samples from the normal,model,and treatment(BXD high-dose)groups.GO functional and KEGG pathway enrichment analyses were conducted on the DEGs.mRNA expression levels of NOD-like receptor thermal protein domain associated protein 3(NLRP3),Caspase-1,and gasdermin D(GSDMD),and protein expression levels of NLRP3,Cleaved Caspase-1,GSDMD-N,and Cleaved IL-1β in gastric tissue were measured by RT-qPCR and Western Blot,respectively.Results(1)Compared with the normal group,the model group showed marked atrophy and thinning of the mucosal epithelium in the gastric antrum and corpus fundus,with a reduction in gland number.Lymphocyte infiltration,lymphoid follicle formation,intestinal metaplasia,and varying degrees of dysplasia were observed.AB-PAS staining of gastric mucosal epithelial cells revealed distinct blue-stained foci and blue-purple foci,with extensive intestinal metaplasia lesions.After drug intervention,pathological changes in the gastric mucosa of the low-dose BXD group showed improvement compared to the model group,but some glandular dilatation and lymphocyte infiltration remained,and AB-PAS staining still showed partial blue-stained foci.The severity of gastric mucosal lesions was significantly alleviated in the positive drug group and the medium-and high-dose BXD groups,with no obvious intestinal metaplasia.AB-PAS staining of gastric mucosal cells in these groups was predominantly red,with rare blue-stained foci.(2)Compared with the normal group,the model group exhibited decreased body mass and gastric SOD content(P＜0.01)and increased gastric pathological scores and levels of MPO,MDA,IL-6,IL-18,TNF-α,and IL-1β(P＜0.01).Compared with the model group,all treatment groups showed increased body mass and gastric SOD content(P＜0.05,P＜0.01).All treatment groups showed decreased levels of gastric IL-6,IL-18,and IL-1β(P＜0.05,P＜0.01).The high-dose BXD and positive drug groups showed decreased gastric pathological scores and levels of TNF-α,MPO,and MDA(P＜0.05,P＜0.01).Although decreasing trends were observed for pathological scores and TNF-α levels in the low-and medium-dose BXD groups and for MPO and MDA levels in the low-dose BXD group,the differences were not statistically significant(P＞0.05).(3)Transcriptomic results revealed 1 032 DEGs(632 up-regulated,400 down-regulated)in the model group vs.the normal group,and 757 DEGs(246 up-regulated,511 down-regulated)in the treatment group vs.the model group.After BXD intervention,554 intersecting DEGs showed a reversion trend:379 DEGs were down-regulated and 175 were up-regulated in the treatment group compared to the model group.These 554 reversed DEGs.KEGG pathway enrichment analysis showed significant enrichment in pathways including other types of O-glycan biosynthesis,PI3K-Akt signaling pathway,NOD-like receptor signaling pathway,and calcium signaling pathway.Cluster analysis indicated significant differential expression of genes in the NOD-like receptor pathway,such as NLRP3,Caspase-1,and GSDMD(P＜0.05).(4)Compared with the normal group,the model group showed increased mRNA expression of NLRP3,Caspase-1,and GSDMD,and increased protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,and Cleaved IL-1β in gastric tissue(P＜0.01).Compared with the model group,all BXD treatment groups showed significantly decreased protein expression of Cleaved Caspase-1,GSDMD-N,and Cleaved IL-1β(P＜0.05,P＜0.01).The medium-and high-dose BXD groups showed significantly decreased mRNA expression of NLRP3,Caspase-1,and GSDMD and protein expression of NLRP3(P＜0.05,P＜0.01).Although decreasing trends were observed for NLRP3,Caspase-1,GSDMD mRNA and NLRP3 protein in the low-dose BXD group,the differences were not statistically significant(P＞0.05).Conclusion BXD ameliorates pathological conditions in CAG rats.Its therapeutic effect may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway,thereby reducing oxidative stress,inflammatory response,and pyroptosis in CAG rats,and protecting the gastric mucosa.关键词
半夏泻心汤/慢性萎缩性胃炎/转录组学/细胞焦亡/作用机制/大鼠Key words
Banxia Xiexin Decoction/chronic atrophic gastritis/transcriptomics/pyroptosis/mechanism of action/rats分类
医药卫生引用本文复制引用
周泽华,胡诚,安叡,王新宏,梁琨..基于转录组学探讨半夏泻心汤对大鼠慢性萎缩性胃炎的作用机制[J].中药新药与临床药理,2026,37(4):644-654,11.基金项目
国家自然科学基金面上项目(82274446,81774183). （82274446,81774183）
