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目的探讨多药耐药基因1(multidrug resistance gene,MDR1)及其表达产物P-糖蛋白(P-glycoprotein,P-gp)在激素耐药系统性红斑狼疮(systemic lupus erythematosus,SLE)患者淋巴细胞的表达及其意义。方法选取初发SLE患者60例,均给予激素和(或)免疫抑制剂治疗6个月,根据治疗后SLEDAI评分及症状改善情况,筛选出激素有效组(n=49)和激素耐药组(n=11),同时以健康体检者30例作为正常对照,RT-PCR检测各组患者外周血淋巴细胞MDR1 mRNA表达,流式细胞术检测P-gp的表达和罗丹明123(rhodamine123,R123)荧光流式细胞术检测P-gp的活性。以环磷酰胺(cyclophosphamide,CTX,100μmol/L)、霉酚酸酯(mycophenolic acid,MPA,100μmol/L)和P-gp特异性封闭剂(Tariquidar,100μmol/L)干预培养激素耐药组患者(n=11)外周血淋巴细胞,R123荧光流式细胞术检测各组P-gp的活性。结果激素耐药组MDR1 mRNA和P-gp的表达明显高于激素有效组(t=3.43,P=0.002)、(t=3.792,P=0.001)和对照组(t=4.54,P<0.001)、(t=4.631,P<0.001);激素耐药组P-gp活性明显高于激素有效组(t=3.062,P=0.019)和对照组(t=5.563,P<0.001)。CTX可以抑制淋巴细胞P-gp活性,MPA抑制P-gp活性的能力明显降低,两者比较差异有统计学意义(t=3.372,P=0.011)。结论 MDR1及其表达产物P-gp参与SLE激素耐药机制的形成,CTX可以通过抑制P-gp活性,在激素耐药SLE的治疗中发挥作用。
Objective To investigate the expression of multidrug resistance gene 1 (MDR1) and its expression product P-glycoprotein (P-gp) in lymphocytes of patients with systemic lupus erythematosus (SLE) The Expression and Significance of. Methods Sixty patients with primary SLE were enrolled. All patients were given hormone and / or immunosuppressive therapy for 6 months. According to SLEDAI score and symptom improvement after treatment, hormone-effective group (n = 49) and hormone-resistant group n = 11). Meanwhile, 30 healthy volunteers were used as normal control. The expression of MDR1 mRNA in peripheral blood lymphocytes was detected by RT-PCR. The expression of P-gp and rhodamine123 (R123) Fluorescence flow cytometry was used to detect the activity of P-gp. The patients in steroid-resistant group were treated with cyclophosphamide (CTX, 100μmol / L), mycophenolic acid (MPA, 100μmol / L) and P-gp specific blocking agent (100μmol / L) (n = 11) peripheral blood lymphocytes were detected by R123 fluorescence flow cytometry P-gp activity. Results The expressions of MDR1 mRNA and P-gp in hormone-resistant group were significantly higher than those in the hormone-effective group (t = 3.43, P = 0.002) (T = 4.631, P <0.001). The activity of P-gp in hormone-resistant group was significantly higher than that in hormone-effective group (t = 3.062, P = 0.019) and control group (t = 5.563, P <0.001) CTX could inhibit the activity of P-gp in lymphocytes, and the ability of MPA to inhibit the activity of P-gp was significantly reduced. There was a significant difference between the two groups (t = 3.372, P = 0.011). Conclusion MDR1 and its expression product P-gp are involved in the mechanism of SLE hormone resistance. CTX can play a role in the treatment of steroid-resistant SLE by inhibiting P-gp activity.