上海交通大学学报（医学版）

›› 2010, Vol. 30 ›› Issue (4): 375-.

• 论著（基础研究） • 上一篇    下一篇

雷帕霉素对PAN肾病小鼠肾脏病变和VEGF及受体表达的影响

王丽华, 顾乐怡, 梁馨月, 严玉澄, 校丽芳, 高嘉元, 张敏芳, 戴慧丽, 倪兆慧, 钱家麒   

  1. 上海交通大学 医学院仁济医院肾脏内科, 上海 200001
  • 出版日期:2010-04-25 发布日期:2010-04-26
  • 通讯作者: 钱家麒, 电子信箱: Jiaqiqian@126.com。
  • 作者简介:王丽华(1983—), 女, 硕士生；电子信箱: isabella-lihuawang@163.com。
  • 基金资助:

    上海市自然科学基金（07JC14037）

Effects of Rapamycin on nephropathy and expression of VEGF and VEGF receptors in PAN nephritic mice

WANG Li-hua, GU Le-yi, LIANG Xin-yue, YAN Yu-cheng, XIAO Li-fang, GAO Jia-yuan, ZHANG Min-fang, DAI Hui-li, NI Zhao-hui, QIAN Jia-qi   

  1. Renal Division, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China
  • Online:2010-04-25 Published:2010-04-26
  • Supported by:

    Natural Science Foundation of Shanghai, 07JC14037

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摘要：

目的 探讨雷帕霉素对嘌呤霉素氨基核苷（PAN）肾病模型小鼠肾脏病变和肾小球VEGF及受体（VEGFR）表达的影响。方法 24只BALB/c小鼠随机分为PAN组（单次尾静脉注射PAN造模，n=8）、雷帕霉素干预组（单次尾静脉注射PAN造模+雷帕霉素干预，n=8）和对照组（单次尾静脉注射PBS, n=8）。各组动物留取24 h尿液，BCA蛋白定量试剂盒测定24 h尿蛋白排泄量。于造模后第10天处死动物取肾脏制备肾组织标本，透射电子显微镜观察各组肾小球足突结构改变；分别采用Real-time PCR、Western blotting和免疫组织化学方法检测各组肾组织VEGF、VEGFR1、VEGFR2 mRNA以及VEGF、VEGFR2蛋白表达。结果 24 h尿蛋白排泄量为PAN组>雷帕霉素干预组>对照组，组间差异均有统计学意义(P<0.05)。电子显微镜观察发现PAN组肾小球上皮细胞足突广泛融合。各组肾组织VEGF、VEGFR1、VEGFR2 mRNA及蛋白表达为PAN组>雷帕霉素干预组>对照组(P<0.05)，且各组VEGF、VEGFR1、VEGFR2 mRNA及VEGF蛋白表达与24 h尿蛋白排泄量呈正相关 (P<0.05)。结论 雷帕霉素能减轻PAN肾病小鼠蛋白尿的程度，作用机制可能与下调肾小球VEGF及其受体基因表达有关。

关键词: 嘌呤霉素氨基核苷肾病, 血管内皮细胞生长因子, 血管内皮生长因子受体, 蛋白尿, 雷帕霉素, 小鼠

Abstract:

Objective To investigate the effects of Rapamycin on nephropathy and expression of vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR) of glomeruli in puromycin amino nuclear glucoside (PAN) nephritic mice models. Methods Twenty-four BALB/c mice were randomly divided into PAN group (model establishment by single injection of PAN via tail vein, n=8), Rapamycin intervention group (model establishment by single injection of PAN via tail vein+Rapamycin intervention, n=8) and control group (single injection of PBS via tail vein, n=8). Twenty-four-hour urine was obtained from each group, and urinary protein excretion was determined by BCA protein assay. Mice were sacrificed 10 days after model establishment, and renal tissue samples were prepared. The structural changes of foot process of glomeruli in each group was observed by transmission electron microscope, and the expression of VEGF, VEGFR1 and VEGFR2 mRNA and VEGF and VEGFR2 protein was detected by Real-time PCR, Western blotting and immunohistochemistry. Results There were significant differences in 24-h urinary protein excretion among groups (P<0.05), with PAN group>Rapamycin intervention group>control group. Foot process infusion in glomeruli was observed by electron microscopy. The expression of VEGF, VEGFR1 and VEGFR2 mRNA and protein in PAN group was the highest, and that in control group was the lowest, with significant differences among groups (P<0.05). The expression of VEGF, VEGFR1 and VEGFR2 mRNA and protein was significantly correlated with 24-h urinary protein excretion in each group (P<0.05). Conclusion Rapamycin can reduce the proteinuria of PAN nephritic mice, and the mechanism may be related to the down-regulation of expression of VEGF and VEGFR of glomeruli.

Key words: puromycin aminonucleoside nephrosis, vascular endothelial growth factor, vascular endothelial cell growth factor receptor, proteinuria, rapamycin, mouse