南蛇藤提取物通过调控Notch-1信号通路对胃癌前病变的影响  

Effect of Celastrus orbiculatus extract on gastric precancerous lesions through the regulation of the Notch-1 signaling pathway

作　　者：文俊凇 潘子威 刘延庆 朱耀东 Wen Junsong;Pan Ziwei;Liu Yanqing;Zhu Yaodong(Dept of Integrative Medicine and Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Dept of Traditional Chinese Medicine,The Affiliated Hospital of Yangzhou University,Yangzhou 225009)

机构地区：[1]安徽医科大学第一附属医院中西医结合肿瘤科,合肥230022 [2]扬州大学附属医院中医科,扬州225009

出　　处：《安徽医科大学学报》2025年第2期313-320,共8页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82274355);安徽省自然科学基金(编号:2208085MH278)。

摘　　要：目的观察南蛇藤提取物(COE)对胃癌前病变(GPL)的影响,并探究其对缺刻基因1(Notch-1)信号通路的作用。方法用复合模型复制法构建GPL大鼠模型,随机分为对照组、模型组和COE低、中、高剂量组[COE 12.5、25、50 mg/(kg·d)],干预4周后取胃组织,免疫组化(IHC)检测黏蛋白(MUC2、MUC5AC和MUC6)、富含亮氨酸重复序列的G蛋白耦联受体5(Lgr5)、增殖细胞核抗原Ki67(Ki67)及Notch-1的表达;聚合酶链式反应(PCR)测定上述黏蛋白的mRNA。N-甲基-N′-硝基-N-亚硝基胍(MNNG)诱导人胃黏膜上皮细胞(GES-1)构建GPL细胞模型,随机分成对照组、模型组和COE低、中、高浓度组(COE 5、10、20μg/ml),相应干预24 h后,倒置显微镜下观察细胞的变化,Western blot法测定Notch-1和Lgr5的表达,免疫荧光(IF)检测Notch-1的表达。结果与对照组相比,模型组胃组织MUC2、Lgr5、Notch-1及Ki67表达升高(P<0.0001),MUC5AC和MUC6表达降低(P<0.0001);与模型组相比,COE各组的MUC2、Lgr5、Notch-1及Ki67表达降低(P<0.01),MUC5AC和MUC6表达增高(P<0.01)。相比对照组,GES-1模型组细胞形态不规则,细胞间连接疏松且排列紊乱;而COE各组较模型组细胞形态更规则、排列更整齐;此外,相比对照组,模型组Lgr5和Notch-1表达升高(P<0.0001),而COE处理后,二者表达则降低(P<0.001)。结论COE能缓解GPL,其机制可能与下调Notch-1信号通路来改善胃黏膜黏液屏障功能及抑制胃黏膜干细胞异常增殖有关。Objective To observe the effect of Celastrus orbiculatus extract(COE)on gastric precancerous lesions(GPL)and to explore its role in the Notch-1 signaling pathway.Methods GPL rat models were established using a composite model replication method,and the rats were randomly divided into a control group,a model group,and COE low,medium and high dose groups[COE at 12.5,25,and 50 mg/(kg·d)].After 4 weeks of intervention,gastric tissue was collected,and immunohistochemistry(IHC)was performed to detect the expression of mucins(MUC2,MUC5AC,and MUC6),Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Proliferating Cell Nuclear Antigen(Ki67),and Notch-1.Polymerase chain reaction(PCR)was used to determine the mRNA levels of the aforementioned mucins.Human gastric epithelial cells(GES-1)were induced with N-Methyl-N′-nitro-N-nitrosoguanidine(MNNG)to establish a GPL cell model.The cells were randomly divided into control,model,and COE low,medium,and high concentration groups(COE at 5,10,and 20μg/ml).After 24 hours of corresponding interventions,changes in cell morphology were observed under an inverted microscope.Western blot was used to measure the expression of Notch-1 and Lgr5,and immunofluorescence(IF)was employed to detect Notch-1 expression.Results Compared to the control group,the expression of MUC2,Lgr5,Notch-1,and Ki67 in the gastric tissue of the model group rats significantly increased(P<0.0001),while the expression of MUC5AC and MUC6 decreased(P<0.0001).In comparison to the model group,the expressions of MUC2,Lgr5,Notch-1,and Ki67 were significantly reduced in the COE groups(P<0.01),while the expression of MUC5AC and MUC6 significantly increased(P<0.01).In the GES-1 model group,the cells exhibited irregular morphology,loose intercellular connections,and disorganized arrangement compared to the control group.In contrast,the cells in the COE groups displayed a more regular morphology and a more organized arrangement than those in the model group.Additionally,compared to the control group,the express

关 键 词：南蛇藤提取物 胃癌前病变 Notch-1信号通路 富含亮氨酸重复序列的G蛋白耦联受体5 黏蛋白 

分 类 号：R285[医药卫生—中药学]