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目的:探讨IQ结构域GTP酶活化蛋白1(IQ domain GTPase-activating protein 1,IQGAP1)对足细胞细胞骨架重组的调节作用.方法:嘌呤霉素(PAN)刺激小鼠足细胞后,运用实时定量PCR和Western blot印迹法分别检测细胞内IQGAP1mRNA和蛋白表达水平,激光共聚焦显微镜观察足细胞骨架F-actin的分布,F-actin肌动蛋白评分系统(CFS)对骨架重组进行分析,并进一步观察上调和下调足细胞IQGAP1表达对PAN诱导的足细胞骨架重组的影响.结果:①与对照组相比,PAN刺激组足细胞内IQGAP1 mRNA和蛋白表达明显下降(P＜0.05),足细胞F-actin排列紊乱,CFS明显升高;②IQGAP1 siRNA进一步抑制IQGAP1表达后,PAN引起的上述足细胞F-actin重组更加明显(P＜0.05);③转染pCantag-myc-IQGAP1质粒促进IQGAP1表达后,PAN诱导的足细胞F-actin排列紊乱显著减轻,CFS明显下降(P＜0.05).结论:IQGAP1能抑制嘌呤霉素诱导的足细胞骨架重组,对维持足细胞正常骨架结构起着重要作用.“,”Objective:To investigate the regulatory role of IQGAP1 in cytoskeletal rearrangement of podocytes.Methods:Conditionally immortalized mouse podocytes were used to perform cell culture and stimulated by puromycin aminonucleoside (PAN).RT-PCR and Western blot analysis were used to measure the level of IQGAP1 mRNA and protein,respectively.The cytoskeleton of F-actin was evaluated by FITC-conjugated phalloidin staining under laser confocal scanning microscope and semi-quantitative system with cortical?F-actin score (CFS) was used to analyze the degree of actin cytoskeleton arrangement.We further explored the changes of cytoskeletal rearrangement after up-and down-regulation of IQGAP1.Results:①when compared with the control group,the expression of IQGAP1 mRNA and protein was significantly decreased after PAN stimulation in mouse podocytes (P＜0.05).PAN stimulation induced cytoskeletal rearrangement including cortical F-actin ring formation,stress fiber attenuation and CFS up-regulation;②the above rearrangement was exacerbated by IQGAP1 siRNA transfection (P＜0.05);③ PAN induced cortical F-actin ring formation and CFS up-regulation was abated after IQGAP1 plasmid transfection (P＜0.05).Conclusion:IQGAP1 can inhibit PAN induced cytoskeleton rearrangement in podocytes and plays an important role in maintaining normal podocyte cytoskeleton.