欢迎来到《四川大学学报(医学版)》 2019年11月1日 星期五
邱兵, 高霞, 崔维静, 等.地塞米松对阿霉素诱导的肾小球足细胞活动力的影响.四川大学学报(医学版),2019,50(2):197-202
地塞米松对阿霉素诱导的肾小球足细胞活动力的影响
Dexamethasone Blocks Adriamycin-induced Podocytes'Mobility via Impacting Nephrin Expression
  
中文关键词:  地塞米松阿霉素足细胞活动力nephrin
英文关键词:DexamethasoneAdriamycinPodocytesMotilityNephrin
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中文摘要:
      目的探讨地塞米松(dexamethasone, Dex)改善阿霉素(adriamycin, ADR)诱导的肾小球足细胞活性的机制。方法将体外培养的小鼠肾小球足细胞分为3组:ADR组,Dex预处理组(Dex+ADR)和空白对照组。采用划痕实验、Transwell实验、异硫氰酸荧光素标记的牛血清白蛋白(FITC-BSA)方法进行肾小球足细胞功能分析。另取SD雄性大鼠72只,随机分为ADR组(尾静脉注射ADR 7.5 mg/kg),Dex治疗组(ADR+Dex,尾静脉注射ADR 7.5 mg/kg后24 h,再注射Dex 1 mg/kg)和对照组(尾静脉注射等量生理盐水),分别给药后7 d、14 d、21 d和28 d收集24 h尿液,测定24 h尿蛋白。采用实时荧光定量PCR和Western blot分别检测nephrin表达变化。电镜下平均足突宽度(FWP)进行相关分析。结果划痕实验和Transwell结果显示,与空白对照组相比,ADR诱导肾小球足细胞活性升高,而Dex预处理后,肾小球足细胞的活力明显下降,与ADR组的差异有统计学意义(P<0.05)。FITC-BSA结果显示,与空白对照组相比,ADR诱导肾病肾小球足细胞FITC-BSA滤过率升高(P<0.05);与ADR组相比,Dex预处理组肾小球足细胞FITC-BSA滤过率降低(P<0.05)。实时荧光定量PCR和Western Blot结果显示,与对照组大鼠比较,ADR诱导的肾病组肾小球足细胞nephrin表达升高(P<0.05),而Dex预处理后,大鼠肾小球足细胞nephrin 表达下调(P<0.05)。电镜下结果显示,ADR组大鼠FWP高于正常组(P<0.01);与ADR组相比,Dex治疗组FWP降低(P<0.01)。与对照组相比,ADR注射14 d开始,大鼠24 h尿蛋白增多(P<0.01),第28天达到峰值(P<0.001)。与ADR组相比,Dex治疗组大鼠第14、21和28天24 h尿蛋白下降(P<0.001)。结论Dex下调nephrin表达,进而拮抗ADR诱导的体外肾小球足细胞活动力升高,参与缓解肾病大鼠的蛋白尿发生。
英文摘要:
      ObjectiveTo explore how dexamethasone (Dex) directly restores kidney podocyte function in adriamycin (ADR)-induced nephrotic model and the effects of Dex on the motility of podocytes, to analyze whether nephrin is a key signal molecule in the process. MethodsThe cultured podocytes were divided into three growps: ADR treated group, ADR+Dex group, blank control group. The analyses of podocytes function were performed using scrape-wound, Transwell migration assays and FITC-BSA. Quantitative real-time PCR and Western blot were used to test the expression of nephrin. Male SD rats were used to generate ADR-induced nephrology model, and randomly divided into three groups: ADR group, ADR+Dex group and normal group. At 7 d, 14 d, 21 d and 28 d after ADR injection, 24 h urine protein was measured as well. Podocyte foot process effacement was observed under transmission electron microscopy. ResultsPodocytes’ motility, permeability of a monolayer of podocytes incubated with FITC-BSA, the expression of nephrin were higher in ADR group than those in blank control group (P<0.05); on the contrary, the indexes above in Dex+ADR group were decreased when compared with ADR group (P<0.05). 24 h urine protein increased significantly at day 14 (vs. normal group P<0.001) and peaked at day 28 in ADR rats (vs. normal group P<0.001), whereas decreased at day 14, 21 and 28 in Dex+ADR group (vs. ADR group, P<0.001). The FWP of ADR-treated rats was greater than normal group and Dex+ADR group (P<0.01). ConclusionDex impacts the expression of nephrin, relieves the enhanced motility induced by ADR and decreases urine protein level.
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