作　　者： ; ; ;

机构地区： 广州医科大学

出　　处： 《中华生物医学工程杂志》 2019年第1期47-52,共6页

摘　　要： 目的 探讨他克莫司联合激素干预,对阿霉素肾病大鼠足细胞分子podocin和nephrin表达的影响.方法 SD大鼠40只,随机取6只作为正常对照组(A组),尾静脉注射等量生理盐水,其余各组均以尾静脉注射阿霉素制备肾病模型,造模4周后,死亡9只,剩余25只随机取1只检测造模情况显示造模成功,24只随机分为4组(n=6):肾病模型组(B组)、激素组(C组)、他克莫司组(D组)、他克莫司±激素组(E组).C组予强的松6 mg·kg-1·d-1灌胃,2次/周;D组予他克莫司0.5 mg·kg-1·d-1灌胃,1次/d;E组同时按上述方法给予强的松和他克莫司;而A、B组则分别给予等量生理盐水灌胃,1次/d.给药后4周处死大鼠,测定24 h尿蛋白定量及血生化;应用实时荧光定量PCR及免疫印迹测定podocin和nephrin的基因和蛋白质的表达.结果 给药4周后,与A组比较,B、C、D、E组尿蛋白、血清白蛋白下降及血胆固醇、尿素氮、肌酐升高(均P<0.05).与B组比较,C、D、E组尿蛋白、尿素氮、胆固醇、肌酐均降低,血清白蛋白升高,病理改变明显减轻.与A组比较,B、C、D组podocin和nephrin的mRNA表达降低(podocin:0.79±0.04、1.48±0.14、1.65±0.23比1.85±0.06,nephrin:1.42±0.33、12.38±1.29、17.55±1.63比23.51±0.06,均P<0.05).C、D、E(podocin:1.83±0.10,nephrin:22.37±3.84)组表达较B组升高,E组与A组比较差异无统计学意义(均P>0.05).两者mRNA表达与尿蛋白均呈负相关(podocin:r=-0.854,nephrin:r=-0.907,均P<0.05).与A组比较,B、C、D组podocin、nephrin蛋白表达降低(podocin:0.96±0.13、1.07 ±0.32、1.89±0.26比2.03±0.37,nephrin:0.69± 0.13、0.86±0.21、1.10±0.31比1.34±0.23,均P<0.05).C、D、E组podocin(1.11±0.28)、nephrin(1.46±0.34)的蛋白表达较B组升高(均P<0.05).nephrin及podocin蛋白表达与尿蛋白呈负相关(r=-0.873、-0.892,均P<0.05).结论 联合应用他克莫司和肾上腺皮质激素,可能是通过改变肾小球滤过屏障分子结构延缓阿霉素肾病大鼠的病理进程. Objective To investigate the effects of tacrolimus and adrenocortical hormone on the expression of podocyte molecules, podocin and nephrin in rats with adriamycin-induced nephropathy. Methods In 40 SD rats, 6 were randomly included as the normal control group (group A) and injected with the same volume of normal saline. The others were all injected with doxorubicin via tail vein to prepare the nephropathy model. At 4 weeks after modeling, 9 rats died, and 1 rat was selected randomly from the remaining 25 to examine the condition of modeling. The examination showed that the model was successfully established. Twenty-four rats were randomly divided into 4 groups (n=6 each): the nephropathy model group (group B), adrenocortical hormone group (group C), tacrolimus group (group D), tacrolimus+ adrenocortical hormone group (group E). Group C was administered with 6 mg·kg-1·d-1 prednisone for 2 times/week. Group D was given 0. 5 mg·kg-1·d-1 tacrolimus by gavage once daily. Group E was given prednisone and tacrolimus as groups C and D. Groups A and B were given the same volume of normal saline, once daily, respectively. The rats were sacrificed at 4 weeks after administration, and the level of 24 h urinary protein and blood biochemistry were measured. The mRNA and protein expression levels of podocin and nephrin were determined by real-time fluorescent quantitative PCR and Western blotting. Results At 4 weeks after administration, the levels of urine protein and serum albumin decreased, whereas the levels of blood cholesterol, BUN and Cr increased in groups B, C, D and E compared with those in group A (all P<0.05). Compared with group B, the levels of urine protein, BUN, cholesterol and Cr decreased in groups C, D and E, whereas the level of serum albumin increased, and the pathological changes were significantly alleviated. Compared with group A, the mRNA expression levels of podocin and nephrin in groups B, C and D decreased (podocin: 0.79±0.04 vs 1.85±0.06, 1.48±0.14 vs 1.85±0.06, 1.65±0.23 vs 1.85±0.06;neph

关 键 词： 他克莫司 激素类 阿霉素肾病 足细胞分子

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