他克莫司对阿霉素肾病大鼠足细胞损伤的修复作用

    Tacrolimus repairs glomerular podocytes injury in rats with adriamycin induced nephropathy

    • 摘要: 目的 探讨他克莫司对阿霉素肾病大鼠足细胞损伤的修复作用。方法 通过阿霉素尾静脉注射建立大鼠微小病变肾病模型,并以他克莫司进行干预。大鼠随机分为对照组、模型组和他克莫司组。每组分别于第0、7、14、21、28、35天采集尿液,检测尿蛋白排泄量,于造模第35天处死大鼠收集肾脏标本。电镜观察各组大鼠足细胞足突融合情况;TUNEL检测法对肾小球进行染色;免疫组化或免疫荧光对WT-1、caspase-3进行定位和半定量检测,观察大鼠足细胞的数量和凋亡。结果 阿霉素尾静脉注射后大鼠尿蛋白显著增加,足细胞数目明显减少,足突广泛融合;与模型组比较,他克莫司组大鼠24 h尿蛋白明显减少,足突融合改善,足细胞数目增多。与对照组比较,模型组大鼠肾小球内caspase-3蛋白表达增加,TUNEL染色加深;与模型组比较,他克莫司组肾小球内caspase-3表达量下降,TUNEL阳性率减少,说明足细胞凋亡减少。结论 他克莫司可修复阿霉素肾病大鼠足细胞损伤,其机制与抑制足细胞凋亡有关。

       

      Abstract: Objective To explore the repair effect of tacrolimus on podocyte injury in rats with adriamycin-induced nephropathy.Methods A rat model of a minimal lesion nephropathy was established by tail vein injection of adriamycin,and tacrolimus was used for intervention.Rats were randomly divided into control group,model group and tacrolimus treatment group.In each group,urine was collected on days 0,7,14,21,28,and 35,urine protein excretion was measured,and rats were sacrificed on day 35 to collect kidney specimens.Electron microscopy was used to observe the fusion of podocyte processes in each group.The glomeruli were stained with TUNEL assay.Wt-1 and caspase-3 were orientated and semi-quantitatively detected by immunohistochemistry or immunofluorescence to observe the podocyte numbers and the apoptosis of podocytes in rats.Results After injection of adriamycin through tail vein,the urine protein of rats increased significantly,the number of podocytes decreased significantly,and the foot podocyte processes were widely fused.Compared with the model group,rats in the tacrolimus treatment group had significantly reduced 24-hour urine protein,improved foot process fusion,and increased podocyte numbers.Compared with the control group,the expression of caspase-3 protein in the glomeruli of the model group was increased,and the TUNEL stain was deepened.Compared with the model group,the expression of caspase-3 in the glomeruli of the tacrolimus treatment group decreased,and the TUNEL positiveness rate decreased,indicating the apoptosis of podocytes decreased.Conclusions Tacrolimus can repair podocyte injury in rats with adriamycin-induced nephropathy,and its mechanism is related to the inhibition of podocyte apoptosis.

       

    /

    返回文章
    返回