三草调胃汤治疗胃癌前病变的疗效与机制研究  

Study on the therapeutic efficacy and mechanism of San Cao Tiao Wei Tang in the treatment of precancerous lesions of gastric cancer

作　　者：郑镔 蔡妍 赵汗青 董祎 陈滨海 陈卫建 ZHENG Bin;CAI Yan;ZHAO Hanqing;DONG Yi;CHEN Binhai;CHEN Weijian(Zhejiang Chinese Medical University,Hangzhou 310053,China;Department of Acupuncture and Moxibustion,The Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310005,China;Department of Oncology,The Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310005,China)

机构地区：[1]浙江中医药大学,杭州310053 [2]浙江中医药大学附属第二医院针灸科,杭州310005 [3]浙江中医药大学附属第二医院肿瘤科,杭州310005

出　　处：《浙江医学教育》2024年第2期111-116,共6页Zhejiang Medical Education

基　　金：2022年浙江省中医药科技计划项目:“三草调胃汤治疗‘胃癌前状态及病变’的多中心临床疗效及作用机制研究”(2022ZX007)。

摘　　要：目的探讨三草调胃汤治疗胃癌前病变(precancerous lesions of gastric cancer,PLGC)的疗效与机制。方法对高通量基因表达数据库中GSE60427数据与前期实验小鼠胃组织芯片数据进行差异分析,筛选重叠基因并预测三草调胃汤治疗PLGC的靶点基因,进行基因集富集分析。构建药物活性相关基因网络与聚类热图,预测三草调胃汤治疗PLGC的靶点为肿瘤坏死因子(tumor necrosis factor,TNF)与载脂蛋白E(apolipoprotein-E,APOE)。采用自身前后对照研究方法,选择2022年9月至2023年6月在浙江中医药大学附属第二医院陈卫建教授门诊治疗的123例PLGC患者为研究对象,均口服三草调胃汤。6个月后观察患者胃黏膜的病理学变化和血清APOE、TNF-α水平变化。结果PLGC胃组织的APOE基因表达水平较正常胃组织升高,三草调胃汤可以降低PLGC胃组织的APOE基因表达。PLGC与高APOE表达时炎症相关通路和脂质代谢通路均高度富集。TNF是三草调胃汤治疗PLGC的作用靶点,且在PLGC中呈现高表达,与APOE存在共表达关系。三草调胃汤治疗后,中、重度慢性萎缩性胃炎和中、重度肠化生患者数量均有所下降,不典型增生患者数量清零,TNF-α和APOE的表达水平均降低(均P<0.05)。结论三草调胃汤对PLGC疗效显著,其机制可能是通过降低TNF-α、APOE水平实现的。Objective To investigate the efficacy and mechanism of San Cao Tiao Wei Tang(SCTWT)in the treatment of precancerous lesions of gastric cancer(PLGC).Methods Differential analysis of GSE60427 data in the Gene Expression Omnibus database and pre-test mouse gastric tissue microarray data was performed to screen overlapping genes and predict the target genes of SCTWT in the treatment of PLGC,and gene set enrichment analysis was performed.Drug activity-related gene network and clustering heat map were constructed,and predicted that the targets of SCTWT for the treatment of PLGC were tumor necrosis factor(TNF)and apolipoprotein-E(APOE).Clinical validation was performed based on these results.From September 2022 to June 2023,123 patients treated at Prof.CHEN Weijian s clinic in The Second Affiliated Hospital of Zhejiang Chinese Medical University were selected for the study using an autologous before and after control method.All patients were orally treated with SCTWT for 6 months,and gastric mucosa pathological changes and the levels of APOE and tumor necrosis factor-α(TNF-α)were observed.Results APOE gene expression levels were higher in PLGC gastric tissues than those in normal gastric tissues,which indicated SCTWT reduced the expression of APOE in PLGC gastric tissues.Inflammation-related pathways and lipid metabolism pathways were highly enriched in PLGC and when APOE was high expressed.TNF was the target of SCTWT in the treament PLGC and was highly expressed in PLGC,with co-expression relationship with APOE.The number of patients with moderate-severe chronic atrophic gastritis or moderate-severe intestinal metaplasia decreased,the number of patients with dysplasia was cleared,and the expression levels of TNF-αand APOE were all reduced after treatment with SCTWT(all P<0.05).Conclusions The efficacy of SCTWT on PLGC is significant,which may be achieved by decreasing the levels of TNF-αand APOE.

关 键 词：三草调胃汤 胃癌前病变 生物信息学 临床疗效 作用机制 

分 类 号：R969[医药卫生—药理学]