[1]姜正艳,陈璇,郑亮,等.基于miR-106b-5p/BTG3轴探讨胃衡汤对甲基硝基亚硝基胍诱导胃癌前病变小鼠的效应机制[J].陕西中医,2026,(1):3-9.[doi:DOI:10.3969/j.issn.1000-7369.2026.01.001]
　JIANG Zhengyan,CHEN Xuan,ZHENG Liang,et al.The therapeutic mechanism of Weiheng decoction on MNNG-induced gastric precancerous lesions in mice based on miR-106b-5p/BTG3 axis[J].,2026,(1):3-9.[doi:DOI:10.3969/j.issn.1000-7369.2026.01.001]
点击复制

基于miR-106b-5p/BTG3轴探讨胃衡汤对甲基硝基亚硝基胍诱导胃癌前病变小鼠的效应机制

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2026年1期
页码:
3-9
栏目:
出版日期:
2026-01-05

文章信息/Info

Title:
The therapeutic mechanism of Weiheng decoction on MNNG-induced gastric precancerous lesions in mice based on miR-106b-5p/BTG3 axis
作者:
姜正艳1; 陈璇1; 郑亮1; 李镇1; 王渊2; YAROV Abdulrakhim2（哈萨克斯坦）; 陆贤燕3
（1.南京中医药大学第二附属医院，江苏 南京 210017；2.陕西中医药大学针灸推拿学院，陕西 咸阳 712046;3.苏州市吴江区中医医院，江苏 苏州 215221)
Author(s):
JIANG Zhengyan1; CHEN Xuan1; ZHENG Liang1; LI Zhen1; WANG Yuan2; YAROV Abdulrakhim2; LU Xianyan3
(1.Second Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Nanjing 210017，China；2.School of Acupuncture and Moxibustion and Massage,Shaanxi University of Traditional Chinese Medicine，Xianyan 712046,China；3.Traditional Chinese Medicine Hospital of Wujiang District,Suzhou 215221,China)
关键词:
胃癌前病变; 胃衡汤; 肿瘤坏死因子-α ; 白细胞介素-6; 转化生长因子-β
Keywords:
Precancerous lesions of gastric cancer; Weiheng decoction; Tumor necrosis factor-α; Interleukin-6; Transforming growth factor-β
分类号:
R 573
DOI:
DOI:10.3969/j.issn.1000-7369.2026.01.001
文献标志码:
A
摘要:
目的：探讨胃衡汤对甲基硝基亚硝基胍（MNNG）诱导的胃癌前病变（PLGC）小鼠的治疗作用及对miR-106b-5p/BTG3轴的调控机制。方法：采用MNNG联合饥饱失常法建立PLGC小鼠模型。将60只小鼠随机分为空白组、模型组、胃衡汤低、中、高剂量组及胃复春组，每组各10只。通过HE染色观察胃黏膜病理变化；ELISA法检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、转化生长因子-β(TGF-β)表达水平；Western blot检测BTG3、Ki67、Bax及Caspase蛋白表达；扫描电镜观察超微结构；RT-qPCR检测miR-106b-5p表达，并验证其与BTG3的靶向关系。结果：胃衡汤可显著改善PLGC小鼠胃黏膜萎缩、肠化生及炎症浸润等病理表现。与模型组相比，胃衡汤可显著降低促炎因子TNF-α、IL-6、IL-1β的表达水平，并升高抗炎因子IL-10水平；显著抑制miR-106b-5p表达，上调其靶基因BTG3蛋白表达，同时降低增殖标志物Ki67表达，促进凋亡蛋白Bax及Caspase-3、Caspase-9的表达，且呈剂量依赖性，高剂量效果最显著。结论：胃衡汤可能通过下调miR-106b-5p/BTG3，解除其对靶基因BTG3的抑制，从而激活BTG3介导的信号通路，抑制炎症反应、促进细胞凋亡并抑制异常增殖，达到改善PLGC的作用。
Abstract:
Objective:To investigate the therapeutic effect of Weiheng decoction on MNNG-induced precancerous lesions of gastric cancer (PLGC) mice and its regulatory mechanism on miR-106b-5p/BTG3 axis.Methods:The PLGC mouse model was established by MNNG combined with irregular feeding.Sixty mice were randomly divided into blank group,model group,Weiheng decoction low,medium and high dose group and positive drug control group,with 10 mice in each group.The pathological changes of gastric mucosa were observed by HE staining.The expression levels of TNF-α,IL-6,IL-1β,IL-10 and TGF-β were detected by ELISA.The expression of BTG3,Ki67,Bax and Caspase protein was detected by Western blot.The ultrastructure was observed by transmission electron microscope.The expression of miR-106b-5p was detected by RT-qPCR,and its targeting relationship with BTG3 was verified.Results:Weiheng decoction can significantly improve the pathological manifestations of gastric mucosal atrophy,intestinal metaplasia and inflammatory infiltration in PLGC mice.Compared with the model group,Weiheng decoction could significantly reduce the expression levels of pro-inflammatory factors TNF-α,IL-6 and IL-1β,and increase the level of anti-inflammatory factor IL-10.It significantly inhibited the expression of miR-106b-5p,up-regulated the expression of its target gene BTG3 protein,decreased the expression of proliferation marker Ki67,and promoted the expression of apoptotic proteins Bax,Caspase-3 and Caspase-9 in a dose-dependent manner,and the effect of high dose was the most significant.Conclusion:Weiheng decoction may relieve the inhibition of target gene BTG3 by down-regulating miR-106b-5p/BTG3,thereby activating BTG3-mediated signaling pathway,inhibiting inflammatory response,promoting apoptosis and inhibiting abnormal proliferation,so as to improve PLGC.

参考文献/References:

[1]YANG F,SUN Z,WANG D,et al.MiR-106b-5p regulates esophageal squamous cell carcinoma progression by binding to HPGD[J].BMC Cancer,2022,22(1):308.
[2]FARRE P L,DUCA R B,MASSILLO C,et al.MiR-106b-5p:A master regulator of potential biomarkers for breast cancer aggressiveness and prognosis[J].Int J Mol Sci,2021,22(20)：156.
[3]薛兴存,郭锐.健脾益气化瘀方配合西药治疗早期胃癌术后疗效观察[J].陕西中医,2012,33(7):843-844.
[4]LI J Q,TIAN J M,FAN X R,et al.miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway[J].Cell Cycle,2020,19(11):1265-1274.
[5]GU H,GU S,ZHANG X,et al.miR-106b-5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3[J].Cancer Med,2019,8(15):6756-6767.
[6]李镇,张雪薇,姜正艳.胃衡汤调控Nrf2-Keap信号通路抑制老年胃癌前病变患者氧化应激反应的临床研究[J].世界中西医结合杂志,2024,19(7):1409-1414.
[7]SHI W B,WANG Z X,LIU H B,et al.Study on the mechanism of Fufang E’jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics[J].J Ethnopharmacol,2023,304:116030.
[8]SUN H,CHEN X.MiR-106b-5p promotes malignant behaviors of cervical squamous cell carcinoma cells by targeting TIMP2[J].Reprod Sci,2022,29(1):203-211.
[9]ZHOU L,WANG W,WANG F,et al.Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma[J].Mol Cancer,2021,20(1):57.
[10]LUAN W,DING Y,XI H,et al.Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4[J].J Exp Clin Cancer Res,2021,40(1):107.
[11]LIU S,CHEN X,ZHANG S,et al.miR106b5p targeting SIX1 inhibits TGFbeta1induced pulmonary fibrosis and epithelialmesenchymal transition in asthma through regulation of E2F1[J].Int J Mol Med,2021,47(3):04855.
[12]CHEN W,ZHANG K,YANG Y,et al.MEF2A-mediated lncRNA HCP5 inhibits gastric cancer progression via miR-106b-5p/p21 axis[J].Int J Biol Sci,2021,17(2):623-634.
[13]CHEN X,CHEN G,CAO X,et al.Downregulation of BTG3 in non-small cell lung cancer[J].Biochem Biophys Res Commun,2013,437(1):173-178.
[14]朱晓琳,朱庆平,李镇.胃衡汤治疗慢性萎缩性胃炎癌前病变的临床疗效[J].名医,2020，1(15):115-116.
[15]WANG L,MO H,JIANG Y,et al.MicroRNA-519c-3p promotes tumor growth and metastasis of hepatocellular carcinoma by targeting BTG3[J].Biomed Pharmacother,2019,118:109267.
[16]李映虹,王刚,汤明杰,等.基于NF-κB信号通路探讨中医药防治胃癌研究进展[J].陕西中医,2025,46(2):268-272.
[17]LI J,CHU Z P,HAN H,et al.Suppression of miR-93-5p inhibits high-risk HPV-positive cervical cancer progression via targeting of BTG3[J].Hum Cell,2019,32(2):160-171.
[18]马佳乐,梁欣奕,张馨元,等.中药调控铁死亡防治胃癌及癌前病变的研究进展[J].中成药,2025,47(3):839-846.
[19]刘天时,于珊珊.胃癌前病变中医药治疗的研究进展[J].现代医学与健康研究电子杂志,2024,8(21):136-141.
[20]赵俊菲,刘小外,刘松江.中医治未病思想应用于胃癌防治的研究进展[J].世界中医药,2024,19(3):444-448.
[21]KOIDE T,MANDAI S,KITAOKA R,et al.Circulating extracellular vesicle-propagated microRNA signature as a vascular calcification factor in chronic kidney disease[J].Circ Res,2023,132(4):415-431.
[22]王文帆,王汉,程义涛,等.中医药治疗胃癌前病变研究进展[J].亚太传统医药,2024,20(1):239-242.
[23]卢雪凤,黄红侠,周权,等.中医药治疗胃黏膜肠上皮化生的研究进展[J].中国中医基础医学杂志,2023,29(12):2123-2127.
[24]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,2024,45(4):446-450.
[25]张杨,齐紫荆,吴媛,等.胃癌前病变的中药治疗研究进展[J].中医药学报,2023,51(4):112-117.
[26]康文婷,时昭红,刘嵩.中医药精准靶向治疗胃癌前病变及相关信号通路研究[J].辽宁中医药大学学报,2023,25(10):91-96.
[27]SAGIR F,ERSOY T N,TOMBUL T,et al.MiR-132-3p,miR-106b-5p,and miR-19b-3p are associated with brain-derived neurotrophic factor production and clinical activity in multiple sclerosis:A pilot study[J].Genet Test Mol Biomarkers,2021,25(11):720-726.
[28]LEE J,KIM H E,SONG Y S,et al.MiR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway[J].Breast Cancer Res Treat,2019,176(1):119-130.
[29]ZHANG T,CHEN Z,YANG X,et al.Circulating miR-106b-5p serves as a diagnostic biomarker for asymptomatic carotid artery stenosis and predicts the occurrence of cerebral ischemic events[J].Vasc Med,2020,25(5):436-442.
[30]HASANI F A,VALIZADEH M,MAZAHERI Z,et al.MiR-106b-5p intensifies the proliferative potential of spermatogonial stem cells as a prerequisite for male infertility treatment[J].Reprod Sci,2022,29(12):3394-3403.
[31]赵江,唐晓龙,朱惠军.加味补中益气汤联合DOX化疗方案治疗胃癌疗效研究[J].陕西中医,2023,44(11):1554-1557.

相似文献/References:

[1]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,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,(1):103.[doi:DOI:10.3969/j.issn.1000-7369.2020.01.028]
[2]刘颖初,汪红兵,王雅欣,等.基于“补气活血”理论探讨胃癌前病变的“炎癌转化”[J].陕西中医,2023,(12):1767.[doi:DOI:10.3969/j.issn.1000-7369.2023.12.022]
　LIU Yingchu,WANG Hongbing,WANG Yaxin,et al.Discussion on “inflammatory and cancer transformation” of precancerous lesions of gastric cancer based on the theory of “invigorating qi and activating blood circulation”[J].,2023,(1):1767.[doi:DOI:10.3969/j.issn.1000-7369.2023.12.022]
[3]宋 健,孟凯强,雷根平,等.名中医沈舒文使用动物类中药治疗胃癌前病变临床经验[J].陕西中医,2024,(2):256.[doi:DOI:10.3969/j.issn.1000-7369.2024.02.024]
[4]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,2024,(4):446.[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,(1):446.[doi:DOI:10.3969/j.issn.1000-7369.2024.04.003]
[5]张高来,闻新丽.基于联合辨证论治胃癌前病变临床思维与经验[J].陕西中医,2024,(8):1101.[doi:DOI:10.3969/j.issn.1000-7369.2024.08.020]
[6]刘 桐,孙鹤员,唐 强,等.基于圆运动理论探析胃癌前病变的病机与治疗[J].陕西中医,2025,46(4):508.[doi:DOI:10.3969/j.issn.1000-7369.2025.04.016]
　LIU Tong,SUN Heyuan,TANG Qiang,et al.Discussion of the pathogenesis and treatment of gastric precancerous lesions based on circular motion theory[J].,2025,46(1):508.[doi:DOI:10.3969/j.issn.1000-7369.2025.04.016]
[7]曹若彤,沈家林,赵唯含.“扶正-通络-解毒”法干预大鼠毒瘀交阻型胃癌前病变作用机制[J].陕西中医,2025,46(11):1449.[doi:DOI:10.3969/j.issn.1000-7369.2025.11.002]
　CAO Ruotong,SHEN Jialin,ZHAO Weihan.Mechanism of action of Fuzheng-Tongluo-Jiedu method in intervening precancerous lesions of gastric cancer in rats with toxin-stasis intermingling syndrome[J].,2025,46(1):1449.[doi:DOI:10.3969/j.issn.1000-7369.2025.11.002]
[8]薛永立,赵唯含,申佳林,等.基于Hedgehog信号通路探讨中药防治胃癌研究进展[J].陕西中医,2025,46(11):1581.[doi:DOI:10.3969/j.issn.1000-7369.2025.11.027]
　XUE Yongli,ZHAO Weihan,SHEN Jialin,et al.Research progress on prevention and treatment of gastric cancer by traditional Chinese medicine based on Hedgehog signaling pathway[J].,2025,46(1):1581.[doi:DOI:10.3969/j.issn.1000-7369.2025.11.027]

备注/Memo

备注/Memo:
973重大基础研究计划项目（2021CB505200）；第七批全国老中医药专家学术经验继承项目（国中医药人教函〔2022〕76号）；江苏省中医药科技发展计划青年人才项目（QN202216）
更新日期/Last Update: 2026-01-08