Janus激酶3/信号转导和转录激活子5信号通路在原发性痛风性关节炎中的表达及其临床意义

Expression and clinical significance of Janus protein tyrosine kinase/signal transducer and activator of transcription signaling pathway in primary gouty arthritis

目的探索Janus激酶3/信号转导和转录激活子5(JAK3/STAT5)信号通路在原发性痛风性关节炎(GA)患者的PBMCs中的表达及临床意义。方法收集50例急性期痛风患者(AG)、50例间歇期痛风患者(IG)及50名健康体检者(HC)的外周血标本、临床资料及实验室检查指标。采用实时荧光定量聚合酶链反应(RT-qPCR)检测JAK3、STAT5a及信号转导及转录激活因子5b(STAT5b)mRNA表达水平;采用ELISA法检测受试者血浆中IL-2浓度。3组间计量资料符合正态分布的采用单因素方差分析,两两比较采用LSD-t检验,非正态分布的采用Mann-Whitney检验或Kruskal-WallisH检验,变量间相关分析采用Spearman相关分析。结果①JAK3、STAT5a及STAT5b的mRNA表达水平在3组间的差异均有统计学意义(F=50.13,P<0.01;F=7.573,P=0.0007;F=12.14,P<0.01),其中HC组JAK3 mRNA表达水平[(606±65)×10^(-4)]显著高于AG组[(103±13)×10^(-4)]和IG组[(114±24)×10^(-4)],差异有统计学意义(P均<0.01),而AG组中STAT5a mRNA表达水平[(89±9)×10^(-4)]明显高于IG组[(59±4)×10^(-4)]和健康体检者组[(61±4)×10^(-4)],差异有统计学意义(P=0.002,P=0.0039),同时健康体检者组的STAT5b mRNA表达水平[(60±5)×10^(-4)]明显低于AG组[(95±7)×10^(-4)]和IG组[(98±7)×10^(-4)],差异有统计学意义(P=0.0002,P<0.01)。②血浆中IL-2浓度在3组间的差异有统计学意义(F=22.87,P<0.01),AG组患者血清IL-2浓度为[(88±8)pg/ml]显著高于IG组[(32±4)pg/ml]和健康体检者组[(44±4)pg/ml],差异有统计学意义(P均<0.01)。③Spearman相关分析显示:在痛风患者中STAT5a、STAT5b的mRNA表达量与中性粒细胞绝对值呈正相关(r=0.282,P<0.05;r=0.257,P<0.05)。结论IL-2/JAK3/STAT5信号通路参与了痛风的发生发展,提示该通路可能是痛风的发病机制之一。

Objective To explore the expression and clinical significance of Janus protein tyrosine kinase/signal transducer and activator of transcription(JAK3/STAT5)signaling pathway in peripheral blood mononuclear cells(PBMCs)of patients with primary gouty arthritis(GA).Methods Peripheral blood,clinical data and laboratory tests were collected from 50 patients with acute gout(AG),50 patients with intermittent gout(IG)and 50 healthy controls(HC).Quantitative real-time-polymerase chain reaction(RT-qPCR)was used to detect mRNA expression level of JAK3/STAT5 related genes(JAK3,STAT5a,STAT5b).Enzyme linked immune sorbent assay(ELISA)was used to detect interleukin-2(IL-2)concentration in subject′s plasma.Measurement data among the three groups that was in accordance with normal distribution was analyzed by one-way analysis of variance,pairwise comparisons using LSD,non-normal distribution data was analyzed by Mann-Whitney test or Kruskal-Wallis H test,and correlation analysis between variables was analyzed using Spearman correlation analysis.Results①The mRNA expression levels of JAK3,STAT5a and STAT5b were significantly different among the three groups(F=50.13,P<0.01;F=7.573,P=0.0007;F=12.14,P<0.01),of which the JAK3 mRNA expression level in the HC group[(606±65)×10^(-4)]was significantly higher than that in the AG group[(103±13)×10^(-4)]and IG group[(114±24)×10^(-4)],and the difference was statistically significant(both P<0.01),while the STAT5a mRNA expression level in the AG group[(89±9)×10^(-4)]was significantly higher than that in the IG group[(59±4)×10^(-4)]and HC group[(61±4)×10^(-4)],and the difference was statistically significant(P=0.002,P=0.0039),and the expression level of STAT5b mRNA in HC group[(60±5)×10^(-4)]was significantly lower than that in AG group[(95±7)×10^(-4)]and IG group[(98±7)×10^(-4)],and the difference was statistically significant(P=0.0002,P<0.0001).②The difference of IL-2 concentration in plasma among the three groups was statistically significant(F=22.87,P<0.01),and the serum IL-2 concentration in the AG group[(87.9±8.4)pg/ml]was significantly higher than that in the IG group[(32±4)pg/ml]and HC group[(44±4)pg/ml],and the difference was statistically significant(both P<0.01).③Spearman correlation analysis showed that the mRNA expression of STAT5a and STAT5b was positively correlated with the absolute value of neutrophils in patients with gout(r=0.282,P<0.05;r=0.257,P<0.05).Conclusion The IL-2/JAK3/STAT5 signaling pathway is involved in the occurrence and development of gout,suggesting that this pathway may play a key role in the pathogenesis of gout.