免疫性血小板减少症的激素耐药与P-糖蛋白表达和功能活性的相关性  

Relation between glucocorticoid-resistance and P-glycoprotein expression and functional activity in immune thrombocytopenia

作　　者：蒋亘乔 魏昱 曹晶晶 程韵枫[2] 王椿[1] JIANG Genqiao;WEI Yu;CAO Jingjing;CHENG Yunfeng;WANG Chun(Department Hematology,Shanghai General Hospital,Shanghai Jiao Tong University,Shanghai 200080,China;Institute of Clinical Science,Zhongshan Hospital,Fudan University,Shanghai 200032)

机构地区：[1]上海交通大学附属第一人民医院血液科,上海200080 [2]复旦大学附属中山医院临床研究院,上海200032

出　　处：《内科理论与实践》2020年第5期341-346,共6页Journal of Internal Medicine Concepts & Practice

基　　金：国家自然科学基金项目(项目编号:81700112)。

摘　　要：目的:探究免疫性血小板减少症(immune thrombocytopenia,ITP)患者外周血淋巴细胞和淋巴细胞亚群中P-糖蛋白(P-glycoprotein,P-gp)的表达和功能活性与肾上腺糖皮质激素(激素)耐药的相关性。方法 :选取确诊的ITP患者25例,根据激素治疗效果分为激素耐药组(n=11)和激素有效组(n=14);同期的健康体检者13名作为对照组,所有研究对象均采用流式细胞术检测外周血淋巴细胞中P-gp的表达和功能活性,并检测各淋巴细胞亚群(CD4+、CD8+和CD19+细胞)中P-gp的功能活性。结果:对照组、激素耐药组和激素有效组之间的淋巴细胞P-gp表达差异无统计学意义;ITP患者淋巴细胞、CD4+T、CD8+T和CD19+B淋巴细胞中P-gp功能活性激素耐药组(92.54%±2.84%、73.46%±11.24%、93.71%±3.46%、72.94%±15.86%)均高于激素有效组(66.09%±9.96%,t=9.45, P<0.001;48.26%±12.79%, t=4.68,P<0.001;73.88%±4.75%, t=9.30,P<0.001;46.19%±23.57%, t=2.96, P=0.005)和对照组(72.56%±8.73%, t=7.78,P<0.001;59.32%±15.41%, t=2.59,P=0.014;81.39%±6.88%, t=5.68,P<0.001;48.77%±25.62%, t=2.63,P=0.013);激素有效组ITP患者CD4+(48.26%±12.79%)和CD8+T淋巴细胞(73.88%±4.75%)中P-gp功能活性均低于对照组(59.32%±15.41%, t=2.15,P<0.001;81.39%±6.88%, t=5.68, P<0.001)。结论:P-gp参与ITP激素耐药机制的形成,检测其表达和功能有助于预测ITP患者激素疗效,并对耐药患者后续治疗提供依据和指导。Objective To investigate the relation between glucocorticoid(GC)-resistance and P-glycoprotein(P-gp) expression and functional activity of peripheral lymphocytes and lymphocyte subsets in immune thrombocytopenia(ITP) patients. Methods Twenty-five ITP patients and 13 healthy controls were enrolled. ITP patients were divided into GC-resistant group(n=11) and GC-responsive group(n=14) according to the effect of GC treatment. Flow cytometry was used to detect P-gp expression and functional activity in peripheral blood lymphocytes and P-gp functional activity in lymphocyte subsets(CD4+, CD8+and CD19+). Results There is no significant difference in expression of P-gp among controls, GC-resistant and GC-responsive groups. The functional activities of P-gp in lymphocytes, CD4+T, CD8+T and CD19+B lymphocytes in GC-resistant group were significantly higher than GC-responsive group(92.54% ±2.84% vs 66.09% ±9.96%, t =9.45;73.46% ±11.24% vs 48.26% ±12.79%, t =4.68;93.71% ±3.46% vs 73.88% ±4.75%, t =9.30;72.94% ±15.86% vs46.19%±23.57%, t=2.96;P<0.05) and controls(92.54%±2.84% vs 72.56%±8.73%, t=7.78;73.46%±11.24% vs 59.32%±15.41%, t=2.59;93.71%±3.46% vs 81.39%±6.88%, t=5.68;72.94%±15.86% vs 48.77%±25.62%, t=2.63;P<0.05);the GC-responsive group had a lower level of P-gp functional activity than controls in CD4+and CD8+T lymphocytes(48.26%±12.79% vs 59.32%±15.41%, t=2.15;73.88%±4.75% vs 81.39%±6.88%, t=5.68;P<0.05). Conclusions P-gp plays an important role in the mechanism of GC-resistance in ITP, suggesting that detecting its expression and functional activity may be helpful to predict the effects of GC in ITP patients and provide guidance for the following treatment of GC-resistant in ITP patients.

关 键 词：免疫性血小板减少症 P-糖蛋白 激素耐药 淋巴细胞 

分 类 号：R558.2[医药卫生—血液循环系统疾病]