益胃饮对N-甲基-N’-硝基-亚硝基胍诱导的大鼠慢性萎缩性胃炎和胃癌的疗效及机制研究  

Study on the Effect and Mechanism of Yiwei Decoction in the Treatment of N-methyl-N’-nitro-Nnitrosoguanidine-induced Chronic Atrophic Gastritis Rats and Gastric Cancer Rats

作　　者：费保莹 吴人照[1] 陈璇[1] 朱佳杰 戴关海[1] 梅茜钰 柴可群[1] FEI Baoying;WU Renzhao;CHEN Xuan;ZHU Jiajie;DAI Guanhai;MEI Xiyu;CHAI Kequn(Zhejiang Academy of Traditional Chinese Medicine,Hangzhou 310007,China)

机构地区：[1]浙江省中医药研究院,杭州310007

出　　处：《中国现代应用药学》2024年第16期2176-2183,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(81703789);浙江省中医药(中西医结合)重点学科建设项目(2017-XK-A24)。

摘　　要：目的探究益胃饮对慢性萎缩性胃炎(chronic atrophic gastritis,CAG)和胃癌的治疗作用及其潜在分子机制。方法采用N-甲基-N’-硝基-亚硝基胍(N-methyl-N’-nitro-N-nitrosoguanidine,MNNG)不同周期灌胃分别诱导大鼠CAG和胃癌模型,益胃饮干预后观察其疗效;结合高通量测序和RT-qPCR检测MNNG诱导肿瘤大鼠胃组织及血液中的转录水平差异。结果益胃饮显著改善MNNG诱导的大鼠CAG和肠化生,显著降低MNNG诱导的大鼠胃十二指肠瘤块质量。高通量测序和RT-qPCR验证结果显示,胃组织中Vcan、BGIG10116_32332、rno-miR-542-3p和血清中rno-miR-363-3p的表达在MNNG诱导后显著升高,而益胃饮可以明显逆转这些现象。同时益胃饮可以不同程度地降低VEGFR、HER-2等胃癌治疗靶点的表达水平。结论益胃饮具有治疗MNNG诱导的CAG和肠化生等胃癌前病变的显著疗效,并能进一步抑制MNNG诱导的大鼠胃十二指肠肿瘤进展,其药效机制可能是通过抑制胃部Vcan、lncRNA BGIG10116_32332和rno-miR-542-3p的过表达,及抑制血液中rno-miR-363-3p的过表达。OBJECTIVE To explore the effect and potential molecular mechanisms of Yiwei Decoction on chronic atrophic gastritis(CAG)and gastric cancer.METHODS N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)was used to induce the model of CAG/gastric precancerous lesions and gastric cancer in rats.Therapeutic effect of Yiwei Decoction after intervention was observed.High-throughput sequencing technology and RT-qPCR were used to detect the change of transcriptome in stomach and blood of MNNG-induced tumor rats.RESULTS Yiwei Decoction significantly ameliorated the MNNG-induced CAG and intestinal metaplasia in rats,and significantly reduced the weight of tumor at gastroduodenal junction.Induction of MNNG obviously increased the mRNA level of Vcan,BGIG10116_32332 and rno-miR-542-3p in rat stomach and rno-miR-363-3p in rat serum,while Yiwei Decoction reversed these change.Moreover,Yiwei Decoction could slightly reduce the expression of gastric cancer therapeutic targets including VEGFR and HER-2.CONCLUSION Yiwei Decoction is effective in the treatment of MNNGinduced CAG and intestinal metaplasia;and it can further inhibit the progression of MNNG induced gastric and duodenal tumors in rats.Its pharmacological mechanism may be achieved by inhibiting the overexpression of Vcan,lncRNA BGIG10116-32332,and rno-miR-542-3p in the stomach,as well as suppressing the overexpression of rno-miR-363-3p in the blood.

关 键 词：益胃饮 治未病 慢性萎缩性胃炎 胃癌前病变 胃癌 分子机制 

分 类 号：R285.5[医药卫生—中药学]