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系统性红斑狼疮患者关节功能变化及外周血单个核细胞分析与不同药物干预作用。

Analysis of changes in joint function and peripheral blood mononuclear cells in patients with systemic lupus erythematosus and intervention effects of different drugs.

机构信息

Department of Rheumatism, the Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Oct;21(19):4423-4430.

Abstract

OBJECTIVE

To investigate the therapeutic effect of drug therapy with cyclophosphamide and leflunomide on the joint function damage of patients with systemic lupus erythematosus (SLE) and its regulatory effects on expression levels of programmed death receptor 1, Notch signaling pathway genes and interferon-inducible protein 10 in peripheral blood mononuclear cells.

PATIENTS AND METHODS

A total of 60 patients with SLE were randomly divided into two groups. They were treated with cyclophosphamide and leflunomide, respectively. The number of painful joints, joint tenderness index, joint swelling index and erythrocyte sedimentation rate of patients before and after treatment were evaluated, and the peripheral blood was collected from patients in the two groups; the peripheral blood mononuclear cells were extracted.

RESULTS

We observed that the number of painful joints, joint tenderness index and joint swelling index in cyclophosphamide group were decreased after treatment (p<0.05), and the erythrocyte sedimentation rate was significantly decreased (p<0.05). The number of painful joints, joint tenderness index and joint swelling index in leflunomide group were decreased after treatment (p<0.05), and the erythrocyte sedimentation rate was significantly decreased (p<0.05). The comparisons of changes in joint functions and erythrocyte sedimentation rates between cyclophosphamide group and leflunomide group after drug therapy showed that the curative effect in leflunomide group was superior to that in cyclophosphamide group (p<0.05). The positive expression rate of peripheral blood mononuclear cell Notch1 in leflunomide group after treatment was significantly decreased, and the curative effect was superior to that in cyclophosphamide group (p<0.05). The comparisons of changes in programmed death receptor 1 of lymphocytes and interferon-inducible protein 10 between cyclophosphamide group and leflunomide group after drug therapy showed that the curative effect in leflunomide group was superior to that in cyclophosphamide group (p<0.05). The comparison of positive expression rate of nuclear factor-κB (NF-κB) in peripheral blood mononuclear cells between the two groups after treatment showed that the curative effect in leflunomide group was superior to that in cyclophosphamide group (p<0.05). There were positive correlations of the expression level of programmed death receptor 1 of peripheral blood lymphocytes in SLE patients with double-stranded DNA (ds-DNA) and SLE disease activity index (p<0.05). There were positive correlations of the expression level of peripheral interferon-inducible protein 10 in SLE patients with ds-DNA and SLE disease activity index (p<0.05).

CONCLUSIONS

This study proved that both leflunomide and cyclophosphamide have therapeutic effects on the joint functions and immune dysfunction of peripheral blood mononuclear cells of SLE patients; however, and the effect of leflunomide is better. There are positive correlations of SLE disease activity index with the Notch signaling pathway genes, programmed death receptor 1 and interferon-inducible protein 10 in peripheral blood mononuclear cells, suggesting that these factors are related to the immune dysfunction of peripheral blood mononuclear cells.

摘要

目的

探讨环磷酰胺和来氟米特联合药物治疗对系统性红斑狼疮(SLE)患者关节功能损害的治疗效果及其对外周血单个核细胞程序性死亡受体 1、Notch 信号通路基因和干扰素诱导蛋白 10 表达水平的调节作用。

患者与方法

将 60 例 SLE 患者随机分为两组,分别采用环磷酰胺和来氟米特治疗,评估患者治疗前后的疼痛关节数、关节压痛指数、关节肿胀指数和红细胞沉降率,并采集两组患者外周血,提取外周血单个核细胞。

结果

我们观察到环磷酰胺组治疗后疼痛关节数、关节压痛指数和关节肿胀指数降低(p<0.05),红细胞沉降率明显降低(p<0.05)。来氟米特组治疗后疼痛关节数、关节压痛指数和关节肿胀指数降低(p<0.05),红细胞沉降率明显降低(p<0.05)。药物治疗后环磷酰胺组与来氟米特组关节功能和红细胞沉降率变化的疗效比较显示,来氟米特组的疗效优于环磷酰胺组(p<0.05)。来氟米特组治疗后外周血单个核细胞 Notch1 的阳性表达率明显降低,疗效优于环磷酰胺组(p<0.05)。药物治疗后环磷酰胺组与来氟米特组淋巴细胞程序性死亡受体 1 和干扰素诱导蛋白 10 变化的疗效比较显示,来氟米特组的疗效优于环磷酰胺组(p<0.05)。治疗后两组外周血单个核细胞核因子-κB(NF-κB)阳性表达率比较显示,来氟米特组的疗效优于环磷酰胺组(p<0.05)。SLE 患者外周血淋巴细胞程序性死亡受体 1 的表达水平与双链 DNA(ds-DNA)和 SLE 疾病活动指数呈正相关(p<0.05)。SLE 患者外周血干扰素诱导蛋白 10 的表达水平与 ds-DNA 和 SLE 疾病活动指数呈正相关(p<0.05)。

结论

本研究证明来氟米特和环磷酰胺均对 SLE 患者关节功能和外周血单个核细胞免疫功能障碍有治疗作用,但来氟米特的效果更好。SLE 疾病活动指数与外周血单个核细胞 Notch 信号通路基因、程序性死亡受体 1 和干扰素诱导蛋白 10 呈正相关,提示这些因素与外周血单个核细胞免疫功能障碍有关。

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