摘要
目的:研究强直性脊柱炎(AS)差异基因的免疫浸润情况,为深入了解AS的免疫相关机制提供理论依据。方法:运用R语言及相关安装包程序对AS差异基因进行基因本体论(GO)及基因通路富集分析(KEGG);通过CIBERSORT反卷积算法对22类免疫细胞在AS中的含量及比例进行分析;通过Coremine Medical及本草组鉴数据库对显著富集的免疫相关的生物学过程及核心靶基因进行中药预测。结果:AS相关的蛋白网络互作枢纽靶基因涉及SNRPG、LSM3、PSMA6、MRPL22、RPL26、COX7C、PSMA4、RPS17、RPL31、SLIRP、NDUFS5、RPS24、NDUFB3、SRP14等14个靶基因,涉及中性粒细胞脱粒、T细胞介导免疫反应等多种途径,与NF-κB转录调控、核糖体生物发生、氧化磷酸化通路密切相关。CIBERSORT反卷积算法对AS的免疫相关性分析中,CD4^(+)T细胞与γδT细胞呈中度正相关,CD8^(+)T细胞与中性粒细胞呈中度负相关。AS组患者血清中单核细胞明显多于正常组,而正常组调节性T细胞明显少于AS组,其中SNRPG、LSM3、PSMA6、MRPL22与单核细胞、调节性T细胞呈负相关,但相关性较弱。雷公藤、蜈蚣、冬虫夏草与AS相关免疫浸润的关系最密切,涉及补肾活血汤、化痰逐瘀散结汤、寄生汤等多种方剂,功效多与清热补虚、补肾健脾、活血通络相关。结论:中性粒细胞、单核细胞、调节性T细胞与AS关系密切,并且CD4^(+)T细胞与γδT细胞具有协同作用,筛选出的雷公藤、蜈蚣、冬虫夏草等中药可能作为其潜在的分子药物来源。
Objective:To study the immune infiltration of differential genes in ankylosing spondylitis(AS),and to provide theoretical basis for in-depth understanding of the immune-related mechanism of AS.Methods:Gene ontology(GO)and gene pathway enrichment analysis(KEGG)of AS differential genes were performed by using R language and related packaging procedures.The content and proportion of 22 kinds of immune cells in AS were analyzed by CIBERSORT deconvolution algorithm.The immune-related biological processes and core target genes were predicted by Coremine Medical and herbal database.Results:AS-related protein network interaction hub target genes involved 14 target genes,including SNRPG,LSM3,PSMA6,MRPL22,RPL26,COX7C,PSMA4,RPS17,RPL31,SLIRP,NDUFS5,RPS24,NDUFB3,SRP14.Results:They involved in neutrophil degranulation,T cell mediated immune response and other pathways,and were closely related to NF-κB transcription regulation,ribosome biogenesis,oxidative phosphorylation pathway.In the immune correlation analysis of AS with CIBERSORT deconvolution algorithm,CD4^(+)T cells were moderately positively correlated with γδT cells,and CD8^(+)T cells were moderately negatively correlated with neutrophils.The serum monocytes in the AS group were significantly more than those in the normal group,while the regulatory T cells in the normal group were significantly less than those in the AS group.Among them,SNRPG,LSM3,PSMA6 and MRPL22 were negatively correlated with monocytes and regulatory T cells,but the correlation was weak.Leigongteng(Tripterygii Wilfordii Radix),Wugong(Scolopendra)and Dongchong Xiacao(Cordyceps)have the closest relationship with AS-related immune infiltration,involving Bushen Huoxue Decoction(补肾活血汤),Huatan Zhuyu Sanjie Decoction(化痰逐瘀散结汤),Jisheng Decoction(寄生汤)and other prescriptions.The efficacy is mostly related to clearing heat and tonifying deficiency,tonifying kidney and invigorating spleen,and promoting blood circulation and dredging collaterals.Conclusion:Neutrophils,monocytes and regulatory T cells are closely related to AS,and CD4^(+)T cells and γδT cells have a synergistic effect.The screened Leigongteng(Tripterygii Wilfordii Radix),Wugong(Scolopendra)and Dongchong Xiacao(Cordyceps)and other traditional Chinese medicines may be used as potential molecular drug sources.
作者
丁灿
沈浮
刘鑫
杨雷
DING Can;SHEN Fu;LIU Xin;YANG Lei(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha Hunan 410007,China;Yongzhou Hospital of Traditional Chinese Medicine,Yongzhou Hunan 425000,China)
出处
《中医药导报》
2022年第4期83-89,104,共8页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
湖南省研究生科研创新项目(CX20210683)。
关键词
强直性脊柱炎
免疫浸润
生物信息学
中药
ankylosing spondylitis
immune infiltration
bioinformatics
traditional Chinese medicine
作者简介
通信作者:刘鑫,E-mail:477279453@qq.com;通信作者:杨雷,E-mail:1169949914@qq.com。
