安徽医科大学学报2026，Vol.61Issue(1)：30-37,8.DOI:10.19405/j.cnki.issn1000-1492.2026.01.006
TLR4通过自噬和氧化应激对胃溃疡小鼠炎症反应的调控机制
The regulatory mechanism of TLR4 on the inflammatory response in mice with gastric ulcers through autophagy and oxidative stress
摘要
Abstract
Objective To investigate the effects of Toll-like receptor 4(TLR4)inhibition on autophagy and oxida-tive stress,as well as its regulatory role and mechanism in the inflammatory response in a mouse model of gastric ul-cer.Methods Sixty adult male Kunming mice were equally divided into five groups:control group,model group,model+TLR4-IN-C34 group,model+TLR4-IN-C34+3-MA group,and model+TLR4-IN-C34+H₂O₂ group.Except for the control group,all groups were administered 40 mg/kg indomethacin via gavage.Treatment groups received injections every three days,and all groups were treated for 30 days.Mice were euthanized by cervical dislocation,and gastric tissues were collected.Gastric ulcer scores were assessed,and pathological changes were evaluated via HE staining and scoring.Serum levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),ad-vanced oxidation protein products(AOPP),and prostaglandin E2(PGE2),as well as gastric tissue levels of malo-ndialdehyde(MDA),superoxide dismutase(SOD),and reduced glutathione(GSH),were measured using ELISA.Western blot analysis was performed to detect the expression of TLR4,microtubule-associated protein 1 light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ,autophagy-related protein 5(Atg5),Beclin-1,nuclear factor erythroid 2-re-lated factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H quinone dehydrogenase 1(NQO1)in gastric tis-sues.Immunofluorescence staining was used to assess LC3-Ⅱ fluorescence intensity in gastric tissues.Results Compared with the control group,the model group exhibited upregulation of ulcer scores,HE staining scores,TLR4,IL-1β,IL-6,TNF-α,and AOPP levels,and downregulation of LC3-Ⅱ fluorescence intensity,PGE2 lev-els,Atg5,Beclin-1,nuclear Nrf2,HO-1,NQO1 levels,and the LC3-Ⅱ/Ⅰ ratio(all P<0.05).Compared with the model group,the model+TLR4-IN-C34 group showed downregulation of ulcer scores,HE staining scores,TLR4,IL-1β,IL-6,TNF-α,and AOPP levels,and upregulation of LC3-Ⅱ fluorescence intensity,PGE2 levels,Atg5,Beclin-1,nuclear Nrf2,HO-1,NQO1 levels,and the LC3-Ⅱ/Ⅰ ratio(all P<0.05).Compared with the model+TLR4-IN-C34 group,the model+TLR4-IN-C34+3-MA group exhibited upregulation of ulcer scores,HE staining scores,IL-1β,IL-6,TNF-α,and AOPP levels,and downregulation of LC3-Ⅱ fluorescence intensity,PGE2 levels,Atg5,Beclin-1,and the LC3-Ⅱ/Ⅰ ratio(all P<0.05).Compared with the model+TLR4-IN-C34 group,the model+TLR4-IN-C34+H₂O₂ group showed upregulation of ulcer scores,HE staining scores,IL-1β,IL-6,TNF-α,and AOPP levels,and downregulation of PGE2 levels and nuclear Nrf2,HO-1,and NQO1 levels(all P<0.05).Conclusion Inhibition of TLR4 ameliorates gastric ulcer symptoms and suppresses the inflammatory response in mice by upregulating autophagy and reducing oxidative stress.关键词
Toll样受体4/自噬/氧化应激/胃溃疡/小鼠/炎症反应Key words
Toll-like receptor 4/autophagy/oxidative stress/stomach ulcers/mice/inflammatory response分类
医药卫生引用本文复制引用
杜进璇,翡罗热·地里夏提,轩秋云..TLR4通过自噬和氧化应激对胃溃疡小鼠炎症反应的调控机制[J].安徽医科大学学报,2026,61(1):30-37,8.基金项目
新疆维吾尔自治区自然科学基金项目(编号:2023D01C429) Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2023D01C429) （编号:2023D01C429）
