| 朱鑫超,陆定其,姚心怡,等.基于全基因组甲基化测序技术探究益气养阴祛瘀方治疗原发性干燥综合征的疗效机制[J].浙江中医药大学学报,2024,48(5):530-540. |
| 基于全基因组甲基化测序技术探究益气养阴祛瘀方治疗原发性干燥综合征的疗效机制 |
| Exploring the Therapeutic Mechanism of Yiqi Yangyin Quyu Prescription in the Treatment of Primary Sjgren’s Syndrome Based on Whole Genome Bisulfite Sequencing Technology |
| DOI：10.16466/j.issn1005-5509.2024.05.002 |
| 中文关键词: 原发性干燥综合征 益气养阴祛瘀方 全基因组甲基化测序 DNA甲基化 非编码RNA 免疫炎症 |
| 英文关键词: primary Sj?gren’s syndrome Yiqi Yangyin Quyu Prescription whole genome methylation sequencing DNA methylation noncoding RNA immune inflammation |
| 基金项目:国家自然科学基金面上项目(82074341) |
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| 中文摘要: |
| [目的] 评价益气养阴祛瘀方治疗原发性干燥综合征(primary Sj?gren’s syndrome，pSS)的疗效，并通过全基因组甲基化测序(whole genome bisulfite sequencing，WGBS)技术研究中医药疗效相关的表观遗传标志。[方法] 纳入50例pSS患者，分为中药组30例和西药组20例，对治疗前及治疗12周后的临床信息进行病情评估，并分析疗效。从中药组中选取3例有效患者，对其中药治疗前后的全血样本进行WGBS，通过甲基化位点分析，差异甲基化关联基因的基因本体(gene ontology，GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)和分子特征数据库(The Molecular Signatures Database，MSigDB)富集分析等，研究疗效相关差异甲基化基因及路径。[结果] 与中药治疗前组比较，中药治疗12周后组干燥综合征疾病活动指数(Sj?gren’s syndrome disease activity index，SSDAI)、血沉(erythrocyte sedimentation rate，ESR)、免疫球蛋白G(immunoglobulin G，IgG)水平显著降低(P<0.05)；与西药治疗前组相比，西药治疗12周后组SSDAI、ESR水平明显下降(P<0.05)。中药治疗12周后组与西药治疗12周后组比较，SSDAI、ESR等指标差异均无统计学意义(P>0.05)。WGBS共识别到29个差异甲基化区域(differentially methylated regions，DMRs)，主要集中在重复元件和蛋白编码基因的位点上，共覆盖了68 个基因，包括了mRNA、长链非编码RNA(long noncoding RNA，lncRNA)和circRNA三种RNA类别。富集分析提示，治疗作用与抗原处理和呈递、干扰素相关通路、辅助性T细胞(helper T cell，Th)1和Th2细胞分化等路径密切相关。[结论] 益气养阴祛瘀方能调节DNA甲基化，从而抑制pSS患者体内免疫应答反应，发挥治疗作用。 |
| 英文摘要: |
| [Objective] To evaluate the efficacy of Yiqi Yangyin Quyu Prescription in the treatment of primary Sj?gren’s syndrome(pSS)，and study the epigenetic markers related to the efficacy of traditional Chinese medicine through whole genome bisulfate sequencing(WGBS)technology. [Methods] Fifty patients with pSS were included， including 30 in Chinese medicine group and 20 in western medicine group.Clinical information before treatment and 12 weeks after treatment was evaluated， and the therapeutic effect was analyzed. Three effective patients were selected from Chinese medicine group and their whole blood samples before and after Chinese medicine treatment were subjected to WGBS. Through methylation site analysis， gene ontology(GO) of differentially methylated genes， Kyoto Encyclopedia of Genes and Genomes(KEGG)， and molecular signature database(MSigDB) enrichment analysis， efficacy-related differentially methylated genes and pathways were identified. [Results] Compared with pre-Chinese medicine treatment group， the group treated with Chinese medicine after 12 weeks showed a significant decrease in Sj?gren’s syndrome disease activity index(SSDAI)， erythrocyte sedimentation rate(ESR)，and immunoglobulin G(IgG) level(P<0.05). Compared with pre-western medicine treatment group， the SSDAI and ESR levels in western medicine treatment group after 12 weeks decreased significantly(P<0.05). There was no statistically significant difference in SSDAI， ESR，and other indicators between the group treated with Chinese medicine after 12 weeks and the group treated with western medicine after 12 weeks(P>0.05). WGBS identified a total of 29 differentially methylated regions(DMRs)， mainly concentrated at the sites of repetitive elements and protein coding genes， covering a total of 68 genes， including three RNA categories: mRNA， long noncoding RNA(lncRNA)，and circRNA. Enrichment analysis suggested that the therapeutic effect was closely related to pathways such as antigen processing and presentation， interferon related pathways， and helper T cell(Th)1 and Th2 cell differentiation. [Conclusion] Yiqi Yangyin Quyu Prescription can regulate DNA methylation， thereby inhibiting the immune response in patients with pSS and exerting therapeutic effects. |
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