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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 investigate the differential expression of peripheral blood leukocytes (TLR9) and the effect of hydroxychloroquine on TLR9 in patients with AS (askylosing spondylitis) and healthy individuals. Methods Sixty AS patients were randomly divided into AS group (30 cases) and hydroxychloroquine treatment group (30 cases). Forty healthy subjects were randomly selected as healthy control group. Healthy control group and AS group were given vitamin C 2 / D, began to reduce to 1 tablet / d after the second month, until the end of 6 months for the observation end; hydroxychloroquine treatment group began to take hydroxychloroquine 2 tablets / d, began to reduce after the first 2 months 1 piece / d, until the end of 6 months for the observation of the end. Before treatment, the expression of TLR9 in peripheral blood lymphocytes, monocytes and neutrophils in each group was detected by flow cytometry 2 months after treatment and 6 months after treatment. Results TLR9 was expressed in peripheral blood lymphocytes, monocytes and neutrophils in all groups, and was mainly expressed in monocytes. TLR9 expression in peripheral blood of AS patients (AS group and hydroxychloroquine treatment group) was positive (P <0.05 or P <0.01). The positive rate of TLR9 in hydroxychloroquine group was significantly lower than that in control group at 2 months and 6 months after drug administration (P <0.05 or P <0.01) ). Conclusion The expression of TLR9 is mainly expressed in peripheral blood mononuclear cells. The expression of TLR9 is up-regulated in peripheral blood of patients with AS, suggesting that the abnormality of TLR9 signaling pathway is related to the pathogenesis of AS. The mechanism of hydroxychloroquine treatment of AS is related to the inhibition of TLR9 expression.