南蛇藤提取物通过抑制有氧糖酵解对大鼠胃癌前病变的影响  

Effects of Celastrus Orbiculatus Extract on Precancerous Lesions of Gastric Cancer in Rats by Inhibiting Aerobic Glycolysis

作　　者：张效泽 朱方圆 刘延庆 朱耀东 ZHANG Xiaoze;ZHU Fangyuan;LIU Yanqing;ZHU Yaodong(The First Affiliated Hospital of Anhui Medical University,Hefei 230000 Anhui,China;Yangzhou University,Yangzhou 225000 Jiangsu,China)

机构地区：[1]安徽医科大学第一附属医院,安徽合肥230000 [2]扬州大学,江苏扬州225000

出　　处：《中药新药与临床药理》2023年第11期1487-1494,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金面上项目(82274355);安徽省自然科学基金面上项目(2208085MH278);安徽高校自然科学研究项目(KJ2020A0215)。

摘　　要：目的观察南蛇藤提取物通过抑制有氧糖酵解过程对大鼠胃癌前病变(Precancerous lesions of gastric cancer,PLGC)的影响,并探讨其可能机制。方法采用复合模型复制法构建大鼠胃癌前病变模型,模型复制成功后,随机分为模型组及南蛇藤提取物低、中、高剂量组(12.5、25、50 mg·kg^(-1)),每组10只,灌胃治疗持续4周后处死大鼠。采用苏木素-伊红(HE)染色观察胃黏膜组织病理学改变,化学比色法检测胃黏膜乳酸含量;免疫组化(IHC)及实时荧光定量聚合酶链反应(Real-time PCR)检测有氧糖酵解标志物己糖激酶2(HK2)、M2型丙酮酸激酶(PKM2)、葡萄糖转运蛋白1(GLUT1)、乳酸脱氢酶A(LDHA)、缺氧诱导因子1α(HIF-1α)及潜在靶点叉头框蛋白O4(FOXO4)的蛋白和mRNA表达。结果与模型组比较,不同剂量的南蛇藤提取物能够部分缓解胃癌前病变大鼠胃黏膜的病变;降低大鼠胃黏膜的乳酸含量(P<0.01);降低HK2、PKM2、GLUT1、LDHA、HIF-1α的蛋白及mRNA表达,提高FOXO4的蛋白及mRNA表达(P<0.05,P<0.01)。结论南蛇藤提取物能够有效改善胃癌前病变大鼠胃黏膜组织病理性改变,纠正大鼠胃黏膜的酸性微环境,其机制可能与抑制有氧糖酵解、上调FOXO4的表达有关。Objective To observe the effect of Celastrus orbiculatus extract(COE)on precancerous lesions of gastric cancer(PLGC)in rats by inhibiting the aerobic glycolysis process and investigate its possible mechanisms.Methods The rat model of precancerous lesions of gastric cancer was established using composite modeling method.After the model was successfully copied,the rats were randomly divided into model group,COE low-,medium-,and highdose groups(12.5,25,50 mg·kg^(-1)),with 10 rats in each group.The intragastrical administration lasted for4 weeks.The histopathological changes of gastric mucosa were observed by hematoxylin-eosin(HE)staining,and the content of lactic acid in gastric mucosa was detected by chemical colorimetry.Immunohistochemistry(IHC)and quantitative real-time PCR were used to detect the protein and mRNA expression levels of hexokinase2(HK2),M2pyruvate kinase(PKM2),glucose transporter-1(GLUT1),lactate dehydrogenase A(LDHA),hypoxia inducible factor 1-α(HIF-1α)and potential target forkhead box protein O4(FOXO4),which are the markers of aerobic glycolysis.Results Compared with the model group,different doses of COE could partially relief PLGC of gastric mucosa in rats,reduce lactic acid content of gastric mucosa in rats(P<0.01),decrease the protein and mRNA expressions of HK2,PKM2,GLUT1,LDHA,HIF-1αand increase the protein and mRNA expressions of FOXO4(P<0.05,P<0.01).Conclusion COE can effectively improve the pathological changes of gastric mucosa in PLGC rats and correct the acidic microenvironment of gastric mucosa in rats.The mechanism may be related to the inhibition of aerobic glycolysis and the up-regulation of the expression of FOXO4.

关 键 词：南蛇藤提取物 胃癌前病变 有氧糖酵解 FOXO4 大鼠 

分 类 号：R285.5[医药卫生—中药学]