安徽医科大学学报2026，Vol.61Issue(3)：462-470,9.DOI:10.19405/j.cnki.issn1000-1492.2026.03.011
FOXO4的表达对南蛇藤提取物抑制有氧糖酵解逆转胃癌前病变的影响
Mechanistic investigation of FOXO4 in Celastrus orbiculatus extract-mediated inhibition of aerobic glycolysis in the therapy of gastric precancerous lesions
摘要
Abstract
Objective To investigate the effects of forkhead box protein O4(FOXO4)expression on gastric pre-cancerous lesions(GPL),and to clarify its mechanism in mediating the therapeutic effect of Celastrus orbiculatus extract(COE)on GPL by regulating aerobic glycolysis.Methods Referring to the previously established com-bined modeling protocol in our research group,a rat model of gastric precancerous lesions(GPL)was constructed through the following procedures:rats were given free access to 170 μg/mL N-methyl-N′-nitro-N-nitrosoguanidine(MNNG)solution for ad libitum drinking,fed with a diet supplemented with 0.03%ranitidine hydrochloride,and treated with a cycling regimen of"2-day feeding followed by 1-day fasting".Specifically,on the afternoon of each fasting day,the rats received intragastric administration of 2%sodium salicylate at a dose of 10 mL/kg body weight.FOXO4-silenced and overexpression model rats were constructed by tail vein injection of plasmids.The rats were randomly divided into control,model,COE,overexpression negative control(OE-NC),FOXO4 overex-pression(OE-FOXO4),OE-FOXO4+COE,silencing negative control(shNC),FOXO4 silencing(shFOXO4)and shFOXO4+COE groups.Gastric mucosal histopathological changes were observed in each group.Lactic acid content in gastric mucosal tissues was detected by colorimetry.The expression levels of FOXO4,HK2,PKM2,LDHA and GLUT1 were evaluated by immunohistochemistry(IHC),and their mRNA levels were determined by RT-PCR.Results Compared with the control group,the COE,OE-FOXO4 and OE-FOXO4+COE groups exhib-ited significantly improved gastric mucosal lesions,reduced lactic acid levels,weakened expression of aerobic glycolysis-related proteins(PKM2,HK2,LDHA,GLUT1),and enhanced FOXO4 expression.The OE-FOXO4+COE group showed the lowest lactic acid level and more pronounced changes in related protein expression com-pared with the COE and OE-FOXO4 groups.In contrast,the shFOXO4 and shFOXO4+COE groups displayed in-creased lactic acid levels,enhanced expression of aerobic glycolysis-related proteins,and reduced FOXO4 expres-sion compared with the model group.Conclusion FOXO4 expression is involved in the inhibitory effect of COE on GPL,possibly by regulating the aerobic glycolysis process.关键词
南蛇藤/提取物/胃癌前病变/叉头框蛋白O4/有氧糖酵解Key words
Celastrus orbiculatus thunb/extract/gastric precancerous lesions/forkhead box O4/aerobic glycoly-sis分类
医药卫生引用本文复制引用
潘子威,文俊凇,姚雪丹,刘延庆,朱耀东..FOXO4的表达对南蛇藤提取物抑制有氧糖酵解逆转胃癌前病变的影响[J].安徽医科大学学报,2026,61(3):462-470,9.基金项目
国家自然科学基金项目(编号:82274355) （编号:82274355）
安徽省高校优秀青年教师培养重点项目(编号:2023-385) National Natural Science Foundation of China(No.82274355) （编号:2023-385）
Key Project for the Cultivation of Outstanding Young Teachers in Colleges and Universities in Anhui Province(No.2023-385) （No.2023-385）
