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目的 探讨他克莫司对阿霉素肾病大鼠肾组织中多药耐药基因1(MDR1)表达的影响.方法 通过单侧肾摘除联合尾静脉重复注射阿霉素的方法构建大鼠肾病模型.模型成功后大鼠共分5组:A组(对照组)、B组(模型组)、C组(激素敏感组)、D组(他克莫司治疗组)、E组(激素耐药组).分别于实验第0周、4周、6周、8周、12周末大鼠内眦采血检测生化指标,大鼠代谢笼收集24 h小便,检测大鼠24 h尿蛋白.用实时荧光定量PCR(RT-PCR)检测肾组织中MDR1的表达.结果 (1)实验第4周、6周、8周末B组大鼠的24 h尿蛋白定量、总胆固醇高于A组(P<0.01),血清白蛋白低于A组(P<0.01);实验第6周、8周末C组大鼠的24 h尿蛋白定量、总胆固醇低于B组(P<0.01),血清白蛋白高于B组(P<0.01);D组大鼠第12周末与第8周末24h尿蛋白、总胆固醇降低(P<0.01),血清白蛋白升高(P<0.01).(2)各组大鼠肾组织中均有MDR1表达,第8周末B组、C组、D组、E组大鼠肾组织MDR1表达均明显高于A组(P<0.05),第12周末D组大鼠肾组织MDR1表达较第8周末降低(P<0.05),第12周末D组肾组织MDR1的表达量较C组降低(P<0.01).结论 逆转阿霉素肾病大鼠肾组织中MDR1的高表达可能是他克莫司治疗激素耐药型肾病综合征作用机制之一,为临床他克莫司治疗激素耐药肾病综合征提供了理论依据.“,”Objective To investigate the effect of tacrolimus on the expression of MDR1 in renal tissue of rats with adriamycin nephropathy. Methods The rat model of nephropathy was established by unilateral nephrectomy combined with adriamycin injection via tail vein. After successful model, the rats were divided into five groups: group A (control group), group B (model group), group C (hormone sensitive group), group D (tacrolimus treatment group), and group E (steroid resistant group). Blood samples were collected at 0, 4, 6, 12 weeks of the experiment. The urine of rats was collected from the metabolic cage for 24 h, to detect 24 h urinary protein in rats. The MDR1 expression in renal tissue was detected by real time PCR (RT-PCR). Results (1)24 h urinary protein and total cholesterol of rats in group B for 4, 6 and 8 weeks were higher than those of group A (P<0.01), serum albumin was lower than that of group A (P<0.01); 24 h urine protein and total cholesterol of rats in group C for 6 weeks and 8 weeks were lower than those of group B (P<0.01), serum albumin was higher than that of group B (P<0.01); 24 h urinary protein and total cholesterol of rats in group D for 12 weeks and 8 weeks decreased (P<0.01), the serum albumin elevated (P<0.01). (2)MDR1 was expressed in renal tissue of rats in each group, MDR1 of renal tissue at the end of the 8 weeks of rats in group B, group C, group D and group E were significantly higher than that in group A (P<0.05), the MDR1 expression of renal tissue in rats of 12 weeks in group D was lower than that of 8 weeks (P<0.05), and was lower than that in group C (P<0.01). Conclusion The reversal of high expression of MDR1 in renal tissue of rats with adriamycin nephropathy may be one of the comprehensive mechanism of tacrolimus in the treatment of steroid resistant nephrotic syndrome, which provides theoretical basis for clinical use of tacrolimus in the treatment of steroid resistant nephrotic syndrome.