类风湿关节炎患者外周血肽基脯氨酰顺反异构酶1与辅助性T细胞17/调节性T细胞分析及维甲酸对其的影响  

The effect and analysis of retinoic acid on the peripheral blood Pin1 and T helper cell 17/regulatory cells of rheumatoid arthritis patients

作　　者：乔丽娟 高惠英[1] 张婷婷[1] 尚莉丽 谢戬芳[1] 温鸿雁[1] 罗静[1] 李小峰[1] Qiao Lijuan;Gao Huiying;Zhang Tingting;Shang Lili;Xie Jianfang;Wen Hongyan;Luo Jing;Li Xiaofeng(Department of Rheumatology and Immunology,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001

出　　处：《中华风湿病学杂志》2021年第6期373-377,共5页Chinese Journal of Rheumatology

基　　金：山西省重点研发计划项目(201803D31130)。

摘　　要：目的探索RA患者外周血肽基脯氨酰顺反异构酶1(Pin1)活性的表达和辅助性T细胞(Th)17/调节性T细胞的数值及相关性,并分析全反式维甲酸(ATRA)对其的作用和影响。方法①对比RA患者治疗前后及健康对照组3组间Pin1表达、及Th17、调节性T细胞绝对计数的差异,采用Kruskal-Wallis秩和检验进行分析;②分析RA初治组患者Pin1表达与其一般资料、活动性指标(如ESR、CRP及DAS28评分),以及Th17、调节性T细胞及部分细胞因子的相关性,采用皮尔逊、Spearman相关检验;③分析RA患者加用小剂量全反式维甲酸(10 mg,每周2次)与羟氯喹等传统免疫抑制剂分别治疗3个月后的外周血Pin1表达及Th17/调节性T细胞的差异,2组间对比采用Mann-Whitney U检验,以P<0.05表示差异具有统计学意义。结果①RA初治组的外周血Pin1活性[13.62(9.16,19.42)]高于健康对照组[8.97(7.62,11.45)](Z=42.82,P<0.05),且Th17[18.28(12.76,24.08)]高于健康对照组[6.04(4.96,7.73),Z=48.83,P<0.05],而调节性T细胞[11.06(5.31,21.87)]低于健康对照组[40.41(24.33,48.52),Z=42.21,P<0.05];②RA初治组外周血Pin1活性与CRP、受累关节的个数、DAS28评分、IL-6及TNF-α呈正相关且差异具有统计学意义(r=0.396,P<0.05;r=0.683,P<0.05;r=0.466,P<0.05;r=0.315,P<0.05;r=0.416,P<0.05),而与调节性T细胞值呈负相关(r=-0.502,P<0.05);③与RA初治组比较,RA用药组Pin1活性[6.94(5.96,8.77)]和Th17[7.38(3.85,11.21)]均有所下降,而调节性T细胞[40.41(17.77,33.47),Z=42.82,P<0.05]较前上升;④与传统药物组相比,维甲酸组的调节性T细胞[28.9(21.73,37.36)]较高,差异具有统计学意义(Z=-2.683,P<0.05),Pin1活性[6.23(5.58,8.75)]有明显下降趋势,但差异无统计学意义(Z=-1.622,P=0.104)。结论RA患者外周血Pin1过表达,Th17增高而调节性T细胞降低,加用ATRA联合其他传统药物治疗可以降低Pin1活性,促进调节性T细胞生长,在一定程度上能更有效改善RA患者疾病活动。Objective To explore the expression of peptidyl prolyl cis-trans isomerase(Pin1)activity in peripheral blood of patients with rheumatoid arthritis(RA)and the value and correlation of T helper cell 17/regulatory cells(Th17/Treg)cells,and to analyze the effect and influence of all-transretinoic acid(ATRA)on it.Methods①Comparing the difference of Pin1 expression and absolute counts of Th17 and Treg between RA patients before and after treatment and healthy control group,Kruskal-Wallis rank sum test was used for analysis.②To analyze the correlation between the expression of Pin1 and its general data,activity indicators[such as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)and disease activity score 28 joints(DAS28)scores],Th17,Treg and some cytokines in RA patients,and to use Pearson and Spearman correlation tests.③To analyze the difference of Pin1 expression and Th17/Treg in peripheral blood of RA patients treated with low-dose all-trans retinoic acid(10 mg twice a week)and traditional immunosuppressants such as hydroxychloroquine for 3 months respectively.Mann-Whitney U test was used for comparison between the two groups,and the difference was statistically significant with(P<0.05).Results①The activity of Pin1 in peripheral blood of the newly treated group of RA was[13.62(9.16,19.42)]higher than that of the healthy control group[8.97(7.62,11.45)](Z=42.82,P<0.05),and Th17 was[18.28(12.76,24.08)]higher than that of the healthy control group[6.04(4.96,4.96)](Z=48.83,P<0.05).Treg[11.06(5.31,21.87)].It was lower than that of healthy control group[40.41(24.33,48.52)](Z=42.21,P<0.05).②the activity of Pin1 in peripheral blood of RA patients was positively correlated with CRP,the number of involved joints,DAS28 score,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)(r=0.396,P<0.05;r=0.683,P<0.05;r=0.466,P<0.05;r=0.315,P<0.05;r=0.416,P<0.05).③Compared with the newly treated RA group,the activity of Pin1[6.94(5.96,8.77),Z=42.82,P<0.05]and Th177.38 decreased[7.38(3.85,11.21),Z=48.83,P<0.05],while

关 键 词：关节炎 类风湿 辅助性T细胞17/调节性T细胞 肽基脯氨酰顺反异构酶1 全反式维甲酸 

分 类 号：R593.22[医药卫生—内科学]