基于DNA甲基化探讨凉血退紫方治疗过敏性紫癜血热妄行证的作用机制  

Discussion on the mechanism of Liangxue Tuizi Formula in the treatment of the syndrome of blood-heat of Henoch-Schonlein purpura based on DNA methylation

作　　者：蔡明阳 苏杭[1] 张博[1] 姜盈盈 刘华[2] 温盈 许爽 任献青[1,2] CAI Mingyang;SU Hang;ZHANG Bo;JIANG Yingying;LIU Hua;WEN Ying;XU Shuang;REN Xianqing(The First Affiliated Hospital of Henan University of CM,Zhengzhou 450000,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学第一附属医院,郑州450000 [2]河南中医药大学,郑州450046

出　　处：《中华中医药杂志》2023年第8期3795-3798,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金联合基金项目(No.U2004107);河南省首批拔尖人才专项基金(No.2019ZYBJ01);河南省中医药科学研究专项课题(No.20-21ZY2107)。

摘　　要：目的:从DNA甲基化层面初步探讨凉血退紫方对于过敏性紫癜(HSP)血热妄行证治疗作用的机制。方法:选取2018年5月至2019年12月诊断为HSP血热妄行证并应用凉血退紫方治疗的患儿与健康体检儿童各5例,收集患儿治疗前后的空腹静脉血与健康儿童的空腹静脉血,应用甲基化芯片进行检测,筛选差异位点并进行分析。结果:凉血退紫方治疗前后血热妄行证患儿共有195个差异基因,其中甲基化程度上调的180个、甲基化程度下调的15个。GO富集分析结果表明凉血退紫方通过调节信号转导、T细胞/B细胞分化等生物过程发挥其干预作用,KEGG通路分析提示差异基因富集于Th17细胞分化、抗原处理与呈递等通路,其中STAT3与CD4甲基化在血热妄行证患儿中甲基化程度下调,经凉血退紫方治疗后其甲基化程度上调。结论:凉血退紫方通过调节Th17细胞分化、抗原处理与呈递等通路,对其异常甲基化DNA发挥双重调控作用,其中对STAT3与CD4甲基化程度的调节可能是其主要作用机制。Objective:To investigate the mechanism of Liangxue Tuizi Formula(LXTZF)in the treatment of the syndrome of blood-heat of Henoch-Schonlein purpura from the perspective of DNA methylation.Methods:The fasting venous blood of 5 children who were diagnosed with the syndrome of blood-heat of HSP in the outpatient department and treated with LXTZF,was collected before and after treatment from May 2018 to December 2019.In addition,the fasting venous blood of 5 healthy children was also collected.All the subjects were detected by a methylation chip.The different DNA methylation sites were screened and analyzed.Results:In the children with the syndrome of blood-heat before and after treatment with LXTZF,there were 195 differential genes,including 180 hypermethylation genes and 15 hypomethylation genes.The results of GO enrichment analysis showed that LXTZF exerted its interventional effects by regulating biological processes such as signal transduction and T cell/B cell differentiation.KEGG pathway analysis showed that the differential genes were enriched in Th17 cell differentiation,antigen processing and presentation,and so on.Furthermore,STAT3 and CD4 methylation was down-regulated in the children with the syndrome of blood-heat,and their methylation was up-regulated after LXTZF treatment.Conclusion:LXTZF plays a dual regulatory role on the abnormally methylated genes of Th17 cells by regulating Th17 cell differentiation,antigen processing and presentation,and other pathways,affecting the processes of immune regulation,proliferation,apoptosis,the regulation of methylation of STAT3 and CD4 genes may be the main mechanism of its therapeutic effect.

关 键 词：过敏性紫癜 血热妄行证 作用机制 甲基化 基因芯片 

分 类 号：R272[医药卫生—中医儿科学]