TLR9在强直性脊柱炎患者外周血白细胞中的表达及羟氯喹的干预效应

Expression of TLR9 in Leucocytes from Patients with Ankylosing Spondylitis and Intervention Effect of Hydroxychloroquine

目的探讨TLR9(Toll-like receptor 9,TLR9)在AS(ankylosing spondylitis,AS)患者和健康人群中外周血白细胞的差异表达及羟氯喹的干预效应。方法将60例AS患者随机分为AS组(30例)和羟氯喹治疗组(30例),随机选取同期的健康体检者40例作为健康对照组,健康对照组和AS组开始服用维生素C 2片/d,于第2个月后开始减量为1片/d,直到6个月底为观察终点;羟氯喹治疗组则开始服用羟氯喹2片/d,于第2个月后开始减量为1片/d,直到6个月底为观察终点。用药前、用药后2个月和用药后6个月分别应用流式细胞术检测各组外周血淋巴细胞、单核细胞和中性粒细胞TLR9的表达。结果 TLR9在各组外周血淋巴细胞、单核细胞和中性粒细胞均有表达,以单核细胞表达为主;AS患者(AS组和羟氯喹治疗组)外周血3种细胞TLR9的阳性表达率均明显高于对照组(P<0.05或P<0.01),羟氯喹治疗组用药后2个月和用药后6个月检测TLR9的阳性表达率明显减低,差异有统计学意义(P<0.05)。结论 TLR9主要表达于外周血单核细胞,AS患者外周血3种细胞表达均上调,提示TLR9信号通路的异常与AS的发病相关,羟氯喹治疗AS的机制与其抑制TLR9的表达有关。

Objective To explore the different expression of Toll-like receptor 9（TLR9） in leukocytes and the intervention effect of hydroxychloroquine in the patients with ankylosing spondylitis（AS）. Methods Sixty patients with AS were randomly divided AS group and hydroxychloroquine group（each n=30）,and 40 health examinees were served as control group simultaneously.AS group and control group were received vitamin C,while hydroxychloroquine group was received hydroxychloroquine.The course of medical treatment was six months.Flow cytometry was used to determine the expression of TLR9 in the peripheral blood lymphocytes,monocytes and polymorphonuclear leukocytes before the treatment and after 2-month and 6-month of the treatment. Results The positive rate of TLR9 in leukocytes of AS patients was significantly higher than that in controls（P〈0.05 or P〈0.01）.After 2-month and 6-month of the treatment,the positive expression of TLR9 in hydroxychloroquine group was significantly decreased,and the difference was statistically significant（P〈0.05）. Conclusions TLR9 is expressed in three kinds of leukocytes（lymphocytes,monocytes and polymorphonuclear leukocytes）,but it is mainly expressed in monocytes. The positive rate of TLR9 in monocytes is significantly increased.The results indicate that abnormal TLR9 signal pathway might be related to the pathogenesis of AS.The mechanism of action of hydroxychloroquine in treatment of AS is correlated with its inhibition of the expression of TLR9.