中国病理生理杂志2025，Vol.41Issue(3)：534-544,11.DOI:10.3969/j.issn.1000-4718.2025.03.014
香砂六君子汤通过抑制NLRP3炎症小体介导的细胞焦亡预防乙醇诱导的大鼠胃溃疡
Xiang-Sha-Liujunzi decoction prevents ethanol-induced gastric ulcer in rats by inhibiting NLRP3 inflammasome-mediated pyroptosis
摘要
Abstract
AIM:This study aimed to investigate whether Xiang-Sha-Liujunzi decoction(XSLJZD)prevents ethanol-induced gastric ulcer(GU)in rats by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation-mediated pyroptosis.METHODS:A total of 60 rats were randomly divided into 5 groups:normal control group,model group,positive control(0.33 mg/kg rabeprazole)group,low-dose(3.40 g/kg)XSLJZD group and high-dose(6.80 g/kg)XSLJZD group,with 12 rats per group.Prior to the induction of GU,all rats received their respective treatments via intragastric gavage for 3 d.The GU model was established in all groups except the normal control group using the anhydrous ethanol method.The ulcer index and ulcer inhibition rate were measured.Hematoxylin-eosin staining was performed to observe pathological changes of gastric tissues,and periodic acid-Schiff staining was used to evaluate the mucus content.Scanning electron microscopy and transmission electron microscopy were employed to inves-tigate ultrastructural changes of gastric tissues.Enzyme-linked immunosorbent assay was conducted to measure the levels of interleukin-4(IL-4),IL-10,IL-1β,IL-18,prostaglandin E2(PGE2)and nitric oxide(NO).Additionally,visible spectrophotometric assay was used to determine the levels of malondialdehyde(MDA),glutathione(GSH)and superoxide dismutase(SOD).The protein levels of NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1,gasdermin D(GSDMD),phosphorylated nuclear factor-κB(p-NF-κB)and phosphorylated NF-κB inhibitor β(p-IκBβ)were assessed using immunofluorescence staining.RESULTS:Compared with model group,XSLJZD significantly alleviated gastric tissue injury,reduced the ulcer index,and enhanced the ulcer inhibition rate in GU rats.Treatment with XSLJZD markedly increased the levels of SOD,GSH,IL-4,IL-10,PGE2 and NO in gas-tric tissue,but significantly decreased the levels of MDA,IL-1β and IL-18.At the molecular level,XSLJZD significantly down-regulated the protein levels of NLRP3,ASC,caspase-1,GSDMD,p-NF-κB and p-IκBβ in gastric tissues.CON-CLUSION:Treatment with XSLJZD demonstrates a significant preventive effect against ethanol-induced GU in rats.Its mechanisms may involve the inhibition of NLRP3 inflammasome activation,reduction of the inflammatory response,pre-vention of pyroptosis in gastric mucosal epithelial cells,and enhancement of antioxidant levels.关键词
香砂六君子汤/胃溃疡/NLRP3炎症小体/炎症/细胞焦亡Key words
Xiang-Sha-Liujunzi decoction/gastric ulcer/NLRP3 inflammasome/inflammation/pyroptosis分类
医药卫生引用本文复制引用
张帆,周璇,卓洪民,陈妍,陈永红,宋厚盼..香砂六君子汤通过抑制NLRP3炎症小体介导的细胞焦亡预防乙醇诱导的大鼠胃溃疡[J].中国病理生理杂志,2025,41(3):534-544,11.基金项目
国家自然科学基金资助项目(No.82374429) （No.82374429）
中华中医药学会青年人才托举工程项目(No.2024-QNRC2-B25) （No.2024-QNRC2-B25）
湖南省自然科学基金资助项目(No.2023JJ30460) （No.2023JJ30460）
湖南省卫生健康高层次人才项目(No.20240304116) （No.20240304116）
