Götzl M, Wallner J, Gsur A, Zöchbauer S, Kovarik J, Balcke P, Pirker R
Clinic for Internal Medicine I and III, University of Vienna Medical School, Austria.
Nephron. 1995;69(3):277-80. doi: 10.1159/000188470.
The MDR1 gene, a multidrug resistance gene, codes for P-glycoprotein which pumps hydrophobic drugs out of the cells. Since cyclosporins also bind to P-glycoprotein and might be pumped by this transmembrane protein, we determined the expression of the MDR1 gene in the lymphocytes of 32 patients with renal transplants. MDR1 RNA expression of lymphocytes was measured by slot blot analysis and compared to the expression of drug-sensitive KB-3-1 cells and multidrug-resistant KB-8-5 cells. MDR1 RNA expression was detected in the lymphocytes of 9 (28%) patients, whereas no expression was seen in the remaining 23 patients. No association between MDR1 RNA expression and transplant function or hematological parameters was observed. However, none of the 6 patients who had transplants for more than 40 months expressed the MDR1 gene in their lymphocytes. In conclusion, expression of the MDR1 gene does occur in lymphocytes of patients with renal transplants and might reduce the immunosuppressive efficacy of cyclosporins through enhanced efflux of cyclosporins.
多药耐药基因MDR1编码P-糖蛋白，该蛋白可将疏水性药物泵出细胞。由于环孢菌素也与P-糖蛋白结合，并可能被这种跨膜蛋白泵出，因此我们测定了32例肾移植患者淋巴细胞中MDR1基因的表达。通过狭缝印迹分析测定淋巴细胞的MDR1 RNA表达，并与药物敏感的KB-3-1细胞和多药耐药的KB-8-5细胞的表达进行比较。在9例（28%）患者的淋巴细胞中检测到MDR1 RNA表达，而其余23例患者未检测到表达。未观察到MDR1 RNA表达与移植功能或血液学参数之间的关联。然而，6例移植超过40个月的患者中，没有一例淋巴细胞表达MDR1基因。总之，肾移植患者的淋巴细胞中确实存在MDR1基因的表达，并且可能通过增强环孢菌素的外排而降低其免疫抑制效果。
