国医大师刘尚义养阴药物组合治疗原发性干燥综合征的靶基因生信分析研究
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摘要
目的:利用生物信息分析方法预测探索国医大师刘尚义养阴药物组合(北沙参、五味子、麦冬、天冬)治疗原发性干燥综合征(pSS)的效应靶基因。方法:从BATMAN-TCM中药化合物数据库搜寻刘尚义养阴药物组合所含成分作用的效应基因数据集A,从公共基因芯片数据库GEO筛选符合纳入条件的人外周血、唾液腺或腮腺组织全基因组RNA芯片(因pSS主要破坏外分泌腺,因此选择样本为pSS患者和正常人的唾液腺或腮腺组织、外周血)利用GCBI在线实验室筛选出pSS与正常组织的差异基因数据集B;分别对上述两个数据集及两者的交集通过GCBI进行GO富集分析、KEGG通路分析以及参与生物功能的蛋白相互作用网络分析(PPI分析)。结果:从符合研究纳入条件的3块SS患者与常人血液、唾液腺或腮腺组织基因芯片数据集最终得到含67个差异性基因的数据集(B),从BATMAN-TCM中药化合物数据库查到该药物组合调节基因1293个(A),交集得到该药物组合治疗pSS的潜在靶基因5个(BAFF、Fas、CMPK2、RSAD2、NMI),后续PPI分析及文献回溯证实这5个基因紧密联系,与病毒感染致的免疫反应及细胞凋亡相关,细胞凋亡反应相关通路密切联系,预示该药物组合有可能通过直接或间接调节以BAFF、Fas、CMPK2、NMI等为主的基因或蛋白表达达到抑制pSS进程的效果。结论:利用生物信息学有助于刘尚义教授养阴中药组合成分针对pSS损害靶器官的效应靶基因进行探索,为下一步实验研究指明核心靶点,提供理论依据。
Objective:To explore the target genes of primary Sj?gren's syndrome(p SS)treated by TCM master LIU Shang-yi with combined Chinese yin-nourishing drugs such as Beishanshen(Radix Glehniae),Wuweizi(Fructus Schisandrae Chinensis),Maidong(Radix Ophiopogonis)and Tiandong(Radix Asparagus).Methods:The effect gene dataset A of LIU Shang-yi's combined yin-nourishing drugs was searched from Chinese Medicine Compound Database BATMAN-TCM,and the whole genome RNA microarray of human peripheral blood,salivary gland or parotid gland was screened from GEO database.The GCBI on-line laboratory was used to screen out difference gene dataset B between pSS and normal tissues.The two datasets and their intersection were analyzed by GCBI for GO enrichment,and KEGG pathway analysis and PPI analysis were also done.Results:The data set B of 67 differentially expressed genes was obtained from three gene chip datasets of p SS patients and normal human blood,salivary gland or parotid gland tissue and 1293 regulatory genes(A)were obtained from the BATMAN-TCM.Five potential target genes(BAFF,Fas,CMPK2,RSAD2,NMI)were got from the intersection.PPI analysis and literature review confirmed that these five genes were closely related,and were closely related to the immune response and apoptosis induced by virus infection.Close relation of apoptosis-related pathways indicated that the combined drugs might directly or indirectly regulate the expressions of genes or protein(mainly BAFF,Fas,CMPK2 and NMI)to inhibit the process of p SS.Conclusion:Bioinformatics is helpful for Professor LIU Shang-yi to explore the combined yin-nourishing drugs on p SS damaging target organs,and provide theoretical basis for further experimental research.
Objective:To explore the target genes of primary Sj?gren's syndrome(p SS)treated by TCM master LIU Shang-yi with combined Chinese yin-nourishing drugs such as Beishanshen(Radix Glehniae),Wuweizi(Fructus Schisandrae Chinensis),Maidong(Radix Ophiopogonis)and Tiandong(Radix Asparagus).Methods:The effect gene dataset A of LIU Shang-yi's combined yin-nourishing drugs was searched from Chinese Medicine Compound Database BATMAN-TCM,and the whole genome RNA microarray of human peripheral blood,salivary gland or parotid gland was screened from GEO database.The GCBI on-line laboratory was used to screen out difference gene dataset B between pSS and normal tissues.The two datasets and their intersection were analyzed by GCBI for GO enrichment,and KEGG pathway analysis and PPI analysis were also done.Results:The data set B of 67 differentially expressed genes was obtained from three gene chip datasets of p SS patients and normal human blood,salivary gland or parotid gland tissue and 1293 regulatory genes(A)were obtained from the BATMAN-TCM.Five potential target genes(BAFF,Fas,CMPK2,RSAD2,NMI)were got from the intersection.PPI analysis and literature review confirmed that these five genes were closely related,and were closely related to the immune response and apoptosis induced by virus infection.Close relation of apoptosis-related pathways indicated that the combined drugs might directly or indirectly regulate the expressions of genes or protein(mainly BAFF,Fas,CMPK2 and NMI)to inhibit the process of p SS.Conclusion:Bioinformatics is helpful for Professor LIU Shang-yi to explore the combined yin-nourishing drugs on p SS damaging target organs,and provide theoretical basis for further experimental research.
引文
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[13]李玉玲,冀林华.老年原发性干燥综合征患者干扰素-γ、Fas、Fas L检测的意义[J].中国老年学,2016,36(14):3536-3537.
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[16]PRUITT HC,DEVINE DJ,SAMANT RS.Roles ofN-Myc and STAT interactor in cancer:From initiation todissemination[J].Int J Cancer,2016,139(3):491-500.
[2]孙红艳,陈慕芝,吕安坤,等.原发性干燥综合征中医体质及证型分布特点研究[J].世界科学技术:中医药现代化,2016,18(12):2148-2153.
[3]PAPAGEORGIOU A,ZIOGAS DC,MAVRAGANICP,et al.Predicting the outcome of Sj?gren's syndrome-associated non-hodgkin's lymphoma patients[J].PLo S One,2015,10(2):e0116189.
[4]郑炜,王颖,刘小平,等.基于中医传承辅助平台对中医药治疗原发性干燥综合征组方用药规律的分析[J].中国实验方剂学杂志,2016,22(17):172-176.
[5]唐东昕.刘尚义常用药对辨析与临证应用[M].北京:科学出版社,2016:175-177.
[6]刘伟,李中燕,田艳,等.北沙参的化学成分及药理作用研究进展[J].国际药学研究杂志,2013,40(3):291-294.
[7]李成荫,汪悦,孙丽霞,等.麦冬多糖对NOD小鼠颌下腺保护作用研究[J].中国免疫学杂志,2014,30(2):198-201.
[8]马育轩,黄艳霞,周海纯,等.五味子现代药理及临床研究进展[J].中医药信息,2014,31(1):125-126.
[9]杨晓慧,吴建春,骆莹滨,等.益气解毒方抑瘤作用及生物信息分析[J].广州中医药大学学报,2018,35(1):135-143.
[10]SIDDIQUI H,CHEN T,ALIKO A,et al.Microbiological and bioinformatics analysis of primary Sj?gren's syndrome patients with normal salivation[J].J OralMicrobiology,2016,8(1):31119.
[11]WANG-RENAULT SF,BOUDAOUD S,NOCTURNE G,et al.Deregulation of micro RNA expression in purified T andB lymphocytes from patients with primary Sj?gren'ssyndrome[J].Ann Rheum Dis,2018,77(1):133-140.
[12]IMGENBERG-KREUZ J,SANDLING JK,BJ?RK A,et al.Transcription profiling of peripheral B-cells in antibody positive primary Sj?gren's syndrome reveals upregulated expression of CX3CR1 and a typeⅠand typeⅡinterferon-signature[J].Scandinavian Journal of Immunology,2018,87(5):e12662.
[13]李玉玲,冀林华.老年原发性干燥综合征患者干扰素-γ、Fas、Fas L检测的意义[J].中国老年学,2016,36(14):3536-3537.
[14]贾媛,张莉芸,张改连,等.长链非编码RNA在免疫调节及风湿性疾病中的作用[J].中华临床免疫和变态反应杂志,2017,11(1):42-47.
[15]MARIA NI,STEENWIJK EC,IJPMA AS,et al.Contrasting expression pattern of RNA-sensing receptors TLR7,RIG-I and MDA5 in interferon-positive and interferon-negative patients with primary Sj?gren's syndrome[J].Annals of the Rheumatic Diseases,2016,76(4):721-725.
[16]PRUITT HC,DEVINE DJ,SAMANT RS.Roles ofN-Myc and STAT interactor in cancer:From initiation todissemination[J].Int J Cancer,2016,139(3):491-500.