自噬相关基因在Janus蛋白酪氨酸激酶抑制剂治疗类风湿关节炎前后患者外周血单个核细胞中的表达及其临床意义  

Expression and clinical significance of autophagy-related genes in peripheral blood mononuclear cells of patients before and after Janus protein tyrosine kinase inhibitors for rheumatoid arthritis

作　　者：廖霞 姚婷 谢泓源 余湘 雷天意 张全波[2] 青玉凤[1] LIAO Xia;YAO Ting;XIE Hong-yuan;YU Xiang;LEI Tian-yi;ZHANG Quan-bo;QING Yu-feng(Department of Rheumatology and Immunology,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,Sichuan,China;Department of Geriatrics,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,Sichuan,China)

机构地区：[1]川北医学院附属医院风湿免疫科,四川南充637000 [2]川北医学院附属医院老年科,四川南充637000

出　　处：《川北医学院学报》2023年第6期736-740,744,共6页Journal of North Sichuan Medical College

基　　金：四川省南充市科技项目(20SXQT0308,20SXCXTD0002)。

摘　　要：目的:探讨自噬相关基因(ATGs)是否参与类风湿关节炎(RA)的发生发展及Janus蛋白酪氨酸激酶(JAK)抑制剂治疗前后的自噬表达变化。方法:收集30例经JAK抑制剂治疗24周的RA患者(RA组)的临床、实验室资料及外周血标本;同时收集30名健康者(HC组)外周血标本作为对照。实时荧光定量PCR检测外周血单个核细胞中自噬相关基因的表达水平。结果:RA组ATG5、Beclin-1、LC-3的mRNA表达水平均高于HC组;ATG16的mRNA表达水平低于HC组(P<0.05)。RA组ATG5表达水平与ESR、hsCRP、SJC、PtGA、DAS-28(ESR)、CCP正相关(P<0.05);ATG12表达水平与hsCRP、CCP正相关(P<0.05);ATG16表达水平与hsCRP、SJC正相关(P<0.05);Beclin-1表达水平与ESR、hsCRP、PtGA、DAS-28(ESR)正相关(P<0.05),与RF-IgG负相关(P<0.05);LC-3表达水平与ESR、hsCRP正相关(P<0.05)。治疗24周后,ATG5、LC-3、Beclin-1的mRNA表达水平均降低,ATG16的mRNA表达水平升高(P<0.05)。结论:自噬相关基因参与了RA发病;托法替布可能通过影响RA患者体内的自噬水平,可作为一种潜在的自噬调节剂。Objective:To explore whether autophagy-related genes(ATGS)are involved in the development of rheumatoid arthritis(RA)and the autophagy expression changes before and after treatment with Janus protein tyrosine kinase(JAK)inhibitors.Methods:Clinical and laboratory data and peripheral blood samples of 30 RA patients treated with JAK inhibitors for 24 weeks(RA group)and 30 healthy people(HC group)were collected,and the expression levels of autophagy-related genes in peripheral blood mononuclear cells were detected by RT-qPCR.Results:The mRNA expression levels of ATG 5,Beclin-1 and LC-3 in RA group were higher than those in HC group,while mRNA expression level of ATG 16 in RA group was lower than that in the HC group(P<0.05).In RA group,ATG5 expression was positively correlated with ESR,hsCRP,SJC,PtGA,DAS-28(ESR)and CCP.ATG12 expression was positively correlated with hsCRP and CCP,ATG16 expression was positively correlated with hsCRP and SJC.Beclin-1 expression was positively correlated with ESR,hsCRP,PtGA and DAS-28(ESR),and negatively correlation with RF-IgG.LC-3 expression was positively correlated with ESR and hsCRP(P<0.05).After 24 weeks of treatment,the mRNA expression levels of ATG5,LC-3 and Beclin-1 decreased,while the mRNA expression levels of ATG16 increased(P<0.05).Conclusion:Autophagy-related genes are involved in the pathogenesis of RA.Tofacitinib may act as a potential autophagy regulator by affecting the level of autophagy in RA patients.

关 键 词：类风湿关节炎 Janus蛋白酪氨酸激酶抑制剂 自噬基因 

分 类 号：R593.22[医药卫生—内科学]