Detection of active P-glycoprotein in systemic lupus erythematosus patients with poor disease control.
Detection of active P-glycoprotein in systemic lupus erythematosus patients with poor disease control.
复制标题
病情控制不佳的系统性红斑狼疮患者活性P-糖蛋白的检测
DOI：
10.3892/etm.2012.667
复制
发表时间：
2012-10
影响因子：
2.7
通讯作者：
Lei TC
中科院分区：
文献类型：
--
作者：
Zhang B;Shi Y;Lei TC
活性P-糖蛋白（P-gp）分子已被证明可以将类固醇转运出外周淋巴细胞，导致系统性红斑狼疮（SLE）患者对系统性类固醇治疗的反应较差。本研究旨在探讨有长期激素治疗史的SLE患者外周血淋巴细胞P-gp表达或活性与疾病控制的相关性。共监测了60例接受全身类固醇治疗超过6个月的SLE患者和30例健康受试者。根据SLE患者的疾病活动性（根据SLEDAI-2000估计），将SLE患者细分为活动性和严重活动性疾病。检测外周血淋巴细胞P-gp表达水平和活性。淋巴细胞，从3例严重活动性SLE患者，与高水平的P-gp表达与环磷酰胺，霉酚酸或大黄素在体外和Rh 123-外排活性进行了测定。SLE患者外周血淋巴细胞P-gp表达水平显著高于健康对照组，且P-gp表达水平与疾病活动度呈正相关。与活动期SLE组相比，重度活动期SLE组P-gp表达显著增加。在体外用100 μM环磷酰胺或100 μM大黄素处理淋巴细胞，诱导平均荧光强度增加2倍，如Rh 123-外排试验所检测。总之，SLE患者外周血淋巴细胞中P-gp的高表达水平导致全身性类固醇对疾病控制不良。大黄素是一种来源于中草药的有效成分，通过抑制P-gp外排功能，具有克服P-gp介导的类固醇耐药的作用。
Active P-glycoprotein (P-gp) molecules have been shown to transport steroids out of peripheral lymphocytes, resulting in poor responses to systemic steroid therapy in patients with systemic lupus erythematosus (SLE). This study was carried out to investigate the correlation between the expression or activity of P-gp in peripheral lymphocytes and disease control in SLE patients with a long history of systemic steroid treatment. A total of 60 SLE patients who had received systemic steroid treatment for longer than 6 months and 30 healthy subjects were monitored. SLE patients were subclassified into those with active and severely active forms of the disease according to their disease activity (estimated by SLEDAI-2000). The expression levels and activity of P-gp in peripheral blood lymphocytes were determined. Lymphocytes, obtained from three patients with severely active SLE, with high levels of P-gp expression were treated with cyclophosphamide, mycophenolic acid or emodin in vitro and Rh123-efflux activity was measured. P-gp expression in the peripheral lymphocytes of the SLE patients was significantly higher compared with that of the healthy controls, and a positive correlation between disease activity and P-gp expression levels was observed in these 60 patients. A significant increase in P-gp expression was observed in the severely active compared with the active SLE group. Treatment of lymphocytes with 100 μM cyclophosphamide or 100 μM emodin in vitro induced up to a 2-fold increase in the mean fluorescence intensity, as detected by the Rh123-efflux assay. In conclusion, the high expression levels of P-gp in the peripheral lymphocytes of SLE patients leads to poor disease control by systemic steroids. Emodin, an active ingredient derived from Chinese herbs, possesses a promising effect for overcoming P-gp-mediated steroid resistance by inhibiting the P-gp efflux function.
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DOI：
10.1093/rheumatology/keq376
发表时间：
2011-05
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Yee CS;Farewell VT;Isenberg DA;Griffiths B;Teh LS;Bruce IN;Ahmad Y;Rahman A;Prabu A;Akil M;McHugh N;Edwards C;D'Cruz D;Khamashta MA;Gordon C
通讯作者：
Gordon C
影响因子：
4.2
作者：
Li, Juan;Liu, Peishu;Zhang, Xiaolei
通讯作者：
Zhang, Xiaolei
影响因子：
4.6
作者：
de la Fuente, H;Baranda, L;González-Amaro, R
通讯作者：
González-Amaro, R
影响因子：
0.7
作者：
Grishanova, AY;Mel'nikova, EV;Lyakhovich, VV
通讯作者：
Lyakhovich, VV
影响因子：
9.3
作者：
Wallace DJ
通讯作者：
Wallace DJ