地塞米松对嘌呤霉素损伤足细胞nephrinmRNA表达的影响及意义  

Effect of dexamethasone on expression of nephrin mRNA in impaired podocytes induced by puromycinaminonucleoside

作　　者：王丽娜[1] 于力[1] 余治奇[1] 张瑶[1] 于生友[1] 

机构地区：[1]广州医学院附属广州市第一人民医院儿科,广州510180

出　　处：《国际医药卫生导报》2012年第11期1551-1554,共4页International Medicine and Health Guidance News

基　　金：广州市科技计划项目（2010Y1-C521）

摘　　要：目的观察嘌呤霉素（PAN）和地塞米松（DEX）干预后足细胞形态及nephrinmRNA表达变化，探讨DEX保护PAN诱导体外培养足细胞损伤的作用机制。方法将体外培养的小鼠肾小球足细胞分为三组，分别为对照组、PAN组和DEX组。对照组加入等体积RPMI-1640培养液培养；PAN组加入PAN（终浓度50mg／L）；DEX组同时加入PAN（终浓度50mg／L）和DEX（终浓度1mmol／L）。培养8h、24h和48h后，相差显微镜下观察足细胞形态变化；用图像处理软件分析各组细胞胞体面积的差异。采用实时荧光定量聚合酶链式反应检测培养24h、48h时足细胞nephrinmRNA表达。结果对照组足细胞形态正常，细胞胞体较大，可见树枝样突起及细胞间形成相互连接；PAN诱导足细胞损伤8h、24h和48h时，足细胞面积均较对照组明显缩小，分别为对照组的75％、46％和27％（P〈0．01），足细胞足突及细胞间连接消失。DEX组在干预8h、24h和48h时，足细胞胞体面积均明显大于PAN组（P〈0．01），部分足细胞可见足突及细胞问连接。PAN组足细胞培养24h和48h时，nephrinmRNA表达较对照组明显下降（P〈O．01）；DEX组干预后24h及48h，足细胞nephrinmRNA表达均较PAN组显著升高（P〈0．01）。结论DEX对PAN诱导足细胞损伤具有保护作用，其作用机制可能与上调足细胞分子nephrinmRNA表达有关。Objective To observe the changes in podocyte morphology and expression of nephrin mRNA after intervention with pummyein aminonueleoside （ PAN ） and then dexamethasone （ DEX ）, and to explore the mechanism of action of of DEX in protection of impaired podocytes caused by PAN. Methods The cultured mouse podocytes were divided into 3 groups： control group （ application of RPMI-1640 with the same volume ）, PAN group （ PAN of 50mg/L ）, and DEX group （ PAN of 50 mg/L plus DEX of 1 μmol/L ）. Podoeyte morphology was observed with phase- contrast microscopy and analyzed with the image software 8 h, 24 h, and 48h after treatment expression of nephrin mRNA was detected by semi-quantitative RT-PCR 24 h and 48h after treatment. Results In the control group normal podocytes with a larger size, ＇branch-shaped＇, and intercellular junction were observed. As compared with the control group, treatment with PAN induced significant shrinkage of podocytes, and the cell size decreased to 75%, 46 % %, and 27% at 8 h, 24 h, and 48 h, respectively （ P〈 0.01 ）, with disappearance of podocyte foot process and intercellular junction. As compared with PAN group, DEX improved the shrinkage of podcytes, and the cell size increased obviously 8 h, 24 h, and 48h after treatment （ P〈 0.01 ）, RT- PCR revealed the expression of nephrin mRNA decreased more significantly in PAN group than in control group at 24 h and 48 h （P〈 0.01 ）. As compared with PAN group, the expression of nephrin mRNA in DEX group was significantly increased at 24 h and 48 h （ P 〈 0.01 ）. Conclusions Dexamethasone has a protective effect on impaired podocytes caused by pummyein aminonueleoside, whose mechanism of action was associated with the upregulation of nephrin mRNA expression in the cells.

关 键 词：足细胞 地塞米松 嘌呤霉素 NEPHRIN 

分 类 号：R965[医药卫生—药理学]