MCP治疗类风湿关节炎合并肺纤维化的转录组学分析  

Transcriptome analysis of MCP in the treatment of rheumatoid arthritis with pulmonary fibrosis

作　　者：王冠 耿立霞[1,2] 白力[3,4] 霍银萍 刘静 马雯[1,2,3,4] WANG Guan;GENG Lixia;BAI Li;HUO Yinping;LIU Jing;MA Wen(Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014040,China;Department of Critical Care Medicine,First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology;Institute of Rheumatology and Immunology,Baotou Medical College;Key Laboratory of Autologous Immunology,Inner Mongolia Autonomous Region)

机构地区：[1]内蒙古科技大学包头医学院,内蒙古包头014040 [2]内蒙古科技大学包头医学院第一附属医院重症医学科 [3]包头医学院风湿免疫研究所 [4]内蒙古自治区自体免疫学重点实验室

出　　处：《包头医学院学报》2024年第9期29-35,51,共8页Journal of Baotou Medical College

基　　金：国家自然科学基金(82160309);内蒙古自治区研究生科研创新资助项目(201-2022403)。

摘　　要：目的:探讨改性柑橘果胶(MCP)在治疗类风湿关节炎合并间质性肺病(RA-ILD)的治疗效果和潜在机制。方法:建立RA-ILD小鼠模型,分为对照组、模型组和MCP治疗组。取肺组织做病理切片。另外一部分肺组织进行转录组测序,并进行后续生物信息学分析。结果:MCP可以改善RA-ILD小鼠肺纤维化的病理变化。筛选出药物干预的核心基因23个,其中9个人类中的同源基因的表达是符合在小鼠中的表达趋势的,分别是LCK、THY1、GZMA、CXCR3、LR10RA、CCL5、CTLA4、CD19、CD5,分析富集功能和通路发现T细胞活化调节、细胞黏附调节、免疫受体活性、Th17细胞分化、Th1和Th2细胞分化等通路在MCP治疗纤维化中扮演重要角色。结论:(1)MCP对RA-ILD小鼠治疗效果确切,明显改善肺部纤维化的严重程度和肺组织炎性细胞浸润程度;(2)有23个核心基因在治疗疾病的过程中发挥了关键作用,其中有9个人类同源基因;(3)核心基因通过T细胞活化调节、细胞黏附调节、免疫受体活性、Th17细胞分化、Th1和Th2细胞分化等来发挥作用。Objective:To investigate the therapeutic effect and potential mechanism of modified citrus pectin(MCP)in the treatment of rheumatoid arthritis with interstitial lung disease(RA-ILD).Methods:The RA-ILD mouse model was established and divided into control group,model group and MCP treatment group.Lung tissue was taken for pathological section.The other part of lung tissue was subjected to transcriptome sequencing and subsequent bioinformatics analysis.Results:MCP could improve the pathological changes of pulmonary fibrosis in RA-ILD mice.A total of 23 core genes for drug intervention were screened,of which the expression of 9 homologous genes in humans was consistent with the expression trend in mice,which were LCK,THY1,GZMA,CXCR3,LR10RA,CCL5,CTLA4,CD19,and CD5.The enrichment functions and pathways revealed that pathways such as T cell activation regulation,cell adhesion regulation,immune receptor activity,Th17 cell differentiation,and Th1 and Th2 cell differentiation played an important role in MCP treatment of fibrosis.Conclusion:(1)MCP has a definite therapeutic effect on RA-ILD mice,which can significantly improve the severity of pulmonary fibrosis and the degree of inflammatory cell infiltration in lung tissue;(2)There are 23 core genes that play a key role in the treatment of diseases,including 9 human homologous genes;(3)Core genes play a role through T cell activation regulation,cell adhesion regulation,immune receptor activity,Th17 cell differentiation,Th1 and Th2 cell differentiation.

关 键 词：改性柑橘果胶 类风湿关节炎 肺纤维化 生物信息学 GAL-3 T细胞活化 

分 类 号：R593.22[医药卫生—内科学] R563[医药卫生—临床医学]