[1]沈家林,许雨晴,曹若彤,等.金果胃康胶囊对胃癌前病变模型大鼠胃黏膜ULK1/AMPK/mTOR信号通路的影响[J].陕西中医杂志,2024,(4):446-450.[doi:DOI:10.3969/j.issn.1000-7369.2024.04.003]
　SHEN Jialin,XU Yuqing,CAO Ruotong,et al.Effect of Jinguo Weikang capsule on ULK1/AMPK/mTOR signaling pathway in gastric mucosa of precancerous lesions of gastric cancer model rats[J].,2024,(4):446-450.[doi:DOI:10.3969/j.issn.1000-7369.2024.04.003]
点击复制

金果胃康胶囊对胃癌前病变模型大鼠胃黏膜ULK1/AMPK/mTOR信号通路的影响
分享到：

《陕西中医》杂志[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年4期
页码:
446-450
栏目:
基础研究
出版日期:
2024-04-05

文章信息/Info

Title:
Effect of Jinguo Weikang capsule on ULK1/AMPK/mTOR signaling pathway in gastric mucosa of precancerous lesions of gastric cancer model rats
作者:
沈家林1; 许雨晴1; 曹若彤1; 郗春华1; 赵唯含2
(1.陕西中医药大学,陕西 咸阳 712046; 2.陕西中医药大学附属医院,陕西 咸阳 712000)
Author(s):
SHEN Jialin; XU Yuqing; CAO Ruotong; XI Chunhua; ZHAO Weihan
(Shaanxi University of Chinese Medicine,Xianyang 712046,China)
关键词:
胃癌前病变;  自噬;  金果胃康胶囊;  UNC-51样激酶1;  5'-单磷酸腺苷活化蛋白激酶;  哺乳动物雷帕霉素靶蛋白;  大鼠
Keywords:
Precancerous lesions of gastric cancer;  Autophagy;  Jinguo Weikang capsules;  ULK1;  AMPK;  mTOR;  Rats
分类号:
R 273
DOI:
DOI:10.3969/j.issn.1000-7369.2024.04.003
文献标志码:
A
摘要:
目的:探讨金果胃康胶囊对胃癌前病变(PLGC)大鼠UNC-51样激酶1(ULK1)/5'-单磷酸腺苷活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的影响。方法:75只SPF级Wistar大鼠,除空白组外,采用MNNG复合造模法建立PLGC大鼠模型,造模成功后运用随机数字表法分为模型组、叶酸组及金果胃康高、中、低剂量组,每组12只。灌胃给药8周后取材。HE染色观察胃黏膜病理学变化,免疫组化法检测ULK1蛋白表达水平,qPCR检测胃组织AMPK、mTOR mRNA表达水平,Western blot检测胃组织AMPK、p-AMPK、mTOR、p-mTOR蛋白表达水平。结果:金果胃康胶囊可显著改善PLGC大鼠胃黏膜萎缩、肠化生、上皮结构、形态紊乱及细胞异型性等病理表现。与模型组比较,金果胃康胶囊能显著上调AMPK、p-AMPK、ULK1的表达水平,下调mTOR、p-mTOR的表达水平(P<0.05),以高剂量组疗效最为显著。结论:金果胃康胶囊可能通过调控ULK1/AMPK/mTOR信号通路促进细胞自噬,修复胃黏膜病变,从而起到防治PLGC的作用。
Abstract:
Objective:To investigate the effect of Jinguo Weikang capsules(JGWK)on the ULK1/AMPK/mTOR signaling pathway in the gastric mucosa of rats with precancerous lesions of gastric cancer(PLGC).Methods:A total of 75 SPF wistar rats were randomly assigned to either the blank or PLGC group.PLGC model rats were subjected to the MNNG composite modeling method and randomly divided into five groups:model,folic acid,low-dose JGWK,medium-dose JGWK,and high-dose JGWK groups.Each group consisted of 12 animals,and they were administered the treatment by gavage daily for 8 weeks.Immunohistochemistry was used to detect the protein expression level of ULK1.qPCR was used to detect the mRNA expression levels of AMPK and mTOR,and Western blot was used to detect the protein expression of AMPK,p-AMPK,mTOR,and p-mTOR in gastric tissue levels.Results:JGWK can improve pathological manifestations in PLGC rats,including gastric mucosal atrophy,intestinal metaplasia,epithelial structure,morphological disorder,and cell atypia.Compared with model group,Jinguo Weikang capsule could significantly up-regulate the expression levels of AMPK,p-AMPK and ULK1,and down-regulate the expression levels of mTOR and p-mTOR(P<0.05).The high-dose group has the most significant effect.Conclusion:JGWK may prevent and treat PLGC by regulating the ULK1/AMPK/mTOR signaling pathway,thereby promoting autophagy and repairing gastric mucosal lesions.

参考文献/References:

[1] SHAH S C,PIAZUELO M B,KUIPERS E J,et al.AGA clinical practice update on the diagnosis and management of atrophic gastritis:Expert review[J].Gastroenterology,2021,161(4):1325-1332.
[2] 王萍,李鹏,陈萦晅,等.中国整合胃癌前病变临床管理指南[J].中国中西医结合消化杂志,2022,30(3):163-183.
[3] 赫捷,陈万青,李兆申,等.中国胃癌筛查与早诊早治指南(2022,北京)[J].中国肿瘤,2022,31(7):488-527.
[4] PIAZUELO M B,BRAVO L E,MERA R M,et al.The colombian chemoprevention trial:20-year follow-up of a cohort of patients with gastric precancerous lesions[J].Gastroenterology,2021,160(4):1106-1117.
[5] LEI J,REN F,LI W,et al.Use of folic acid supplementation to halt and even reverse the progression of gastric precancerous conditions:A meta-analysis[J].BMC Gastroenterology,2022,22(1):370.
[6] 张声生,唐旭东,黄穗平,等.慢性胃炎中医诊疗专家共识意见(2017)[J].中华中医药杂志,2017,32(7):3060-3064.
[7] 王思慈,李园,李萍,等.中医药治疗慢性萎缩性胃炎的多途径作用机制[J].中国实验方剂学杂志,2023,29(19):193-202.
[8] 陈丽,信建军,陈鹏.益胃汤合麦门冬汤对胃阴亏虚型慢性胃炎患者的临床疗效[J].中成药,2022,44(7):2157-2161.
[9] 刘佰林,胡金霞,马小强.补气化积汤联合序贯疗法治疗老年HP阳性慢性萎缩性胃炎气虚血瘀型疗效研究[J].陕西中医,2023,44(9):1223-1226.
[10] 冉静纯.基于细胞自噬的金果胃康胶囊对胃癌前病变大鼠胃黏膜保护作用的研究[D].咸阳:陕西中医药大学,2020.
[11] 张兴旺,马艳梅,朱静.早期胃癌及癌前病变组织中LC3、Ki-67、SOX9的表达及临床意义[J].陕西医学杂志,2020,49(11):1519-1522.
[12] 丁霞,苏泽琦,沈洪,等.慢性胃炎“炎癌转化”病证结合大鼠模型建立中的难点问题及应对策略[J].北京中医药大学学报,2020,43(12):973-979.
[13] 刘婷,彭敏,刘倩倩,等.胃癌前病变大鼠病证结合模型的构建与评价[J].中华中医药杂志,2021,36(6):3624-3627.
[14] LIU W Z,XIE Y,LU H,et al.Fifth Chinese national consensus report on the management of helicobacter pylori infection[J].Helicobacter,2018,23(2):e12475.
[15] 李兆申.慢性萎缩性胃炎的早筛、早诊、早治与胃癌的预防[J].中华消化杂志,2021,41(Z1):5-8.
[16] 中华医学会肿瘤学分会,中华医学会杂志社.中华医学会胃癌临床诊疗指南(2021版)[J].中华医学杂志,2022,102(16):1169-1189.
[17] 于莹,张功,韩涛,等.临床常用中成药辅助治疗慢性萎缩性胃炎的网状Meta分析[J].中草药,2022,53(6):1790-1800.
[18] 陈洁,王文丽,钱赟达,等.四君子汤合丹参饮加减治疗高分期萎缩性胃炎的临床疗效及对血清胃蛋白酶原、血液流变学的影响[J].中药材,2023,46(4):1021-1025.
[19] 杨柳,李泽,高云霄,等.胃癌与慢性萎缩性胃炎的差异基因与中药治疗的生信分析及系统评价[J].中成药,2022,44(5):1649-1655.
[20] 张华峰,魏星,张杨.健脾益气法治疗慢性萎缩性胃炎机制研究进展[J].陕西中医,2023,44(6):808-810,814.
[21] 景琛,宋健,王医,等.沈舒文教授辨治慢性萎缩性胃炎的学术思想与临床经验[J].云南中医学院学报,2022,45(4):35-38.
[22] 黄毓娟,沈舒文,宋健,等.金果胃康胶囊治疗胃黏膜上皮内瘤变患者的临床研究[J].中国临床药理学杂志,2020,36(5):486-489.
[23] JIA M,YUE X,SUN W,et al.ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation[J].Science Advances,2023,9(22):e4993.
[24] 王长亮,田文静,黄景荣,等.长链非编码RNA C16orf89在胃癌组织中的表达及对胃癌细胞增殖和侵袭的影响[J].陕西医学杂志,2023,52(6):635-639,644.
[25] BATTAGLIONI S,BENJAMIN D,WALCHLI M,et al.mTOR substrate phosphorylation in growth control[J].Cell,2022,185(11):1814-1836.
[26] 赵唯含,周莹,许雨晴,等.益气活血法通过miR216b/Beclin1介导萎缩性胃炎癌前病变自噬的机制[J].中国实验方剂学杂志,2023,29(10):117-122.
[27] GONZALEZ A,HALL M N,LIN S C,et al.AMPK and TOR:The yin and yang of cellular nutrient sensing and growth control[J].Cell Metabolism,2020,31(3):472-492.

相似文献/References:

[1]胡跃强,陈 炜,祝美珍,等.清热化瘀方通过调控自噬相关基因P62/LC3保护大鼠脑缺血再灌注损伤*[J].陕西中医杂志,2020,(4):429.
　HU Yueqiang,CHEN Wei,ZHU Meizhen,et al.Protective effect of Qingre Huayu prescription against cerebral ischemia-reperfusion injury by regulating autophagy-related gene P62/LC3 in rats[J].,2020,(4):429.
[2]欧阳雅蓉,傅为武,黄彩依,等.自噬在高血压靶器官损害中的作用及中医药治疗研究进展*[J].陕西中医杂志,2020,(11):1669.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.040]
[3]蔺焕萍,王 峰,周晓燕,等.李守朝教授治疗胃癌前病变临证经验拾萃[J].陕西中医杂志,2021,(1):103.[doi:DOI:10.3969/j.issn.1000-7369.2020.01.028]
　LIN Huanping,WANG Feng,ZHOU Xiaoyan,et al.Professor LI Shouchao's experience in the treatment of precancerous lesions of gastric cancer[J].,2021,(4):103.[doi:DOI:10.3969/j.issn.1000-7369.2020.01.028]
[4]沈玉珏.黄芪多糖抑制缺氧/复氧损伤乳鼠心肌细胞凋亡与自噬机制研究[J].陕西中医杂志,2021,(5):561.[doi:DOI:10.3969/j.issn.1000-7369.2020.05.004]
　SHEN Yujue.Mechanism of astragalus polysaccharides inhibiting cardiomyocyte apoptosis and autophagy in neonatal rats injured by hypoxia/reoxygenation[J].,2021,(4):561.[doi:DOI:10.3969/j.issn.1000-7369.2020.05.004]
[5]林增海,陆 军,王凯松.槲皮素对5-FU诱导的结直肠癌SW480细胞耐药及自噬调控机制研究[J].陕西中医杂志,2021,(10):1338.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.004]
　LIN Zenghai,LU Jun,WANG Kaisong.Regulatory mechanism of quercetin on resistance and autophagy of 5-FU induced colorectal cancer SW480 cells[J].,2021,(4):1338.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.004]
[6]方锦颖,王一冲,神原优滋(日本),等.基于网络药理学和分子对接探究肾康注射液治疗糖尿病肾病作用机制[J].陕西中医杂志,2021,(12):1798.[doi:DOI:10.3969/j.issn.1000-7369.2020.12.039]
[7]何佳宁,王佩娟.中药治疗早发性卵巢功能不全机制研究进展[J].陕西中医杂志,2022,(10):1481.[doi:DOI:10.3969/j.issn.1000-7369.2022.10.040]
　HE Jianing,WANG Peijuan.Research progress on the mechanism of traditional Chinese medicine in the treatment of premature ovarian insufficiency[J].,2022,(4):1481.[doi:DOI:10.3969/j.issn.1000-7369.2022.10.040]
[8]何妙嬴,张燚格,柳冬冬,等.电针内关预处理对心肌缺血再灌注损伤大鼠心肌PI3K/Akt通路的影响[J].陕西中医杂志,2023,(3):298.[doi:DOI:10.3969/j.issn.1000-7369.2023.03.006]
　HE Miaoying,ZHANG Yige,LIU Dongdong,et al.Effect of electroacupuncture Neiguan pretreatment on myocardial PI3K/Akt pathway in rats with myocardial ischemia reperfusion injury[J].,2023,(4):298.[doi:DOI:10.3969/j.issn.1000-7369.2023.03.006]
[9]夏雨果,陈 秋,高 坪,等.三才连梅颗粒通过Nrf2/HO-1信号通路对糖尿病小鼠生精功能的影响[J].陕西中医杂志,2023,(4):421.[doi:DOI:10.3969/j.issn.1000-7369.2023.04.003]
　XIA Yuguo,CHEN Qiu,GAO Ping,et al.Effects of Sancai Lianmei granule on the spermatogenesis of diabetic mice through Nrf2/HO-1 signaling pathway[J].,2023,(4):421.[doi:DOI:10.3969/j.issn.1000-7369.2023.04.003]
[10]白 俊,赵晓鹏,王海静,等.补肾活血法调控PI3K/AKT/mTOR通路修复卵巢颗粒细胞自噬损伤机制研究[J].陕西中医杂志,2023,(5):547.[doi:DOI:10.3969/j.issn.1000-7369.2023.05.001]
　BAI Jun,ZHAO Xiaopeng,WANG Haijing,et al.Research on the mechanism of repairing autophagic damage in ovarian granulosa cells by regulating PI3K/AKT/mTOR pathway by tonifying kidney and activating blood[J].,2023,(4):547.[doi:DOI:10.3969/j.issn.1000-7369.2023.05.001]

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81804082)
更新日期/Last Update: 2024-04-10