世界中医药

作者	单位
顾沐恩1,黄艳2,刘雅楠2,刘慧荣1,2,黄儒德2,吴璐一1,2,彭广彬1,李国娜3,李璟1,吴焕淦1,2	1 上海中医药大学附属岳阳中西医结合医院，上海，200437； 2 上海市针灸经络研究所，上海，200030； 3 上海中医药大学，上海，201203

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中文摘要:

目的：观察隔药饼灸及隔姜灸治疗慢性萎缩性胃炎（CAG）的临床疗效，探讨艾灸对CAG相关癌前病变外周血DNA甲基化谱的影响。方法：选取2018年5月至2020年10月上海中医药大学附属岳阳中西医结合医院针灸科收治的CAG患者70例作为研究对象，随机分为隔药饼灸组和隔姜灸组，每组35例，2组患者均选取中脘、气海、双侧足三里、双侧内关穴进行治疗。比较2组治疗前后中医症状评分、光镜下胃黏膜组织病理学变化，评价2组的临床疗效，并选取每组治疗前后患者全血样本各2例，采用全基因组甲基化测序，结合生物信息学分析，观察外周血DNA甲基化位点和甲基化状态的变化。结果：1）治疗后，2组中医症状总积分均较治疗前显著降低（均P<0.01），隔药饼灸组胃脘疼痛、食欲减退症状积分低于隔姜灸组（均P<0.01），隔姜灸组烧心、反胃症状积分低于隔药饼灸组（均P<0.01）；隔药饼灸组临床总有效率为87.88%，隔姜灸组为78.79%，差异无统计学意义（P>0.05）。治疗后2组胃黏膜的萎缩、肠化病变程度及隔药饼灸组的炎症程度有明显改善（P<0.05）。隔药饼灸组胃镜病理总体有效率82.14%，隔姜灸组总体有效率69.57%，差异无统计学意义（P>0.05）。2）CG序列环境下，治疗前后隔药饼灸组共有176个差异甲基化基因，隔姜灸组有652个差异甲基化基因。隔药饼灸组治疗前后差异甲基化区域（DMR）锚定启动子区域相关基因涉及的KEGG通路包括cAMP、AMPK和核因子κB信号通路、泛素介导的蛋白水解等，隔姜灸组涉及的KEGG通路包括mTOR和HIF-1信号通路、代谢通路、细胞凋亡等。结论：隔药饼灸和隔姜灸可改善慢性萎缩性胃炎患者临床症状，减轻胃黏膜萎缩、肠化生等病理状态；隔药饼灸在改善患者胃脘疼痛、食欲减退症状更具优势，而隔姜灸在改善患者烧心、反胃症状更优。艾灸能影响CAG患者外周血全基因组DMR的DNA甲基化水平，这可能是艾灸对CAG的表观遗传调控机制之一。

English Summary:

To observe the clinical efficacy of herb-partitioned moxibustion (HM) and ginger-partitioned moxibustion (GM) in the treatment of chronic atrophic gastritis (CAG) and explore the effect of moxibustion on DNA methylation in peripheral blood of CAG-related precancerous lesions.Methods:Seventy CAG patients who were treated in the Acupuncture and Moxibustion Department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine from May 2018 to October 2020 were randomly divided into an HM group and a GM group，with 35 cases in each group.“Zhongwan” (CV 12)，“Qihai” (CV 6)，bilateral “Zusanli” (ST 36)，and bilateral “Neiguan” (PC 6) were selected for treatment in both groups.The clinical efficacies were evaluated by comparing the symptom scores of traditional Chinese medicine (TCM) and the gastric mucosal changes under gastroscopy before and after treatment.Whole blood samples from two patients in each group were collected before and after treatment.Genome-wide methylation sequencing and bioinformatics analysis were used to observe the changes of DNA methylation sites and methylation status in the peripheral blood.Results:1) The post-treatment TCM symptom scores were lower than pre-treatment ones in both groups (both P<0.01).The scores of gastric pain and loss of appetite were lower in the HM group and heartburn and nausea scores were lower in the GM group after treatment (both P<0.01).The total clinical effective rates were 87.88% and 78.79% in the HM group and the GM group，respectively (P>0.05).The histopathological changes in the gastric mucosa atrophy and intestinal metaplasia of the two groups as well as the degree of mucosal inflammation in the HM group were improved after treatment (P<0.05).The total effective rates of gastroscopy were 82.14% and 69.57% in the HM group and the GM group (P>0.05).2) In the CG sequencing environment，there were 176 and 652 differentially methylated genes in the HM group and the GM group，respectively，before and after treatment.In the HM group，the KEGG pathways of genes involved in the differentially methylated region (DMR)-anchored promoter region before and after treatment included cAMP，AMPK，and NF-κB signaling pathways，ubiquitin-mediated proteolysis，etc.，while in the GM group，the KEGG pathways included mTOR and HIF-1 signaling pathways，metabolic pathway，cell apoptosis，etc.Conclusion:Both HM and GM can improve the clinical symptoms of CAG patients and alleviate pathological conditions such as gastric mucosal atrophy and intestinal metaplasia.HM is advantageous in improving the symptoms of gastric pain and loss of appetite，while GM is potent in improving the symptoms of heartburn and nausea.Moxibustion can affect the DNA methylation levels in the DMR of the whole genome in the peripheral blood of CAG patients，which may be one of the epigenetic regulatory mechanisms of moxibustion against CAG.

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