剪切应力增加致肾小管上皮细胞megalin／cubilin mRNA表达的变化及效应  

Effects of increased shear stress on the expression of megalin/cubilin mRNA in cultured renal tubular epithelial cells

作　　者：柳飞[1] 黄颂敏[1] 蒲丽君[1] 付平[1] 

机构地区：[1]四川大学华西医院肾脏内科,四川成都610041

出　　处：《生物医学工程与临床》2008年第5期412-415,共4页Biomedical Engineering and Clinical Medicine

基　　金：四川省科技厅攻关项目（05SG022-018-4）

摘　　要：目的检测剪切应力作用下肾小管上皮细胞megalin/dcubilin mRNA表达的变化，探讨糖尿病肾病（diabetic nephropathy，DN）早期肾小管间质病变的发生机制。方法应用流室系统（flow chamber）提供0．5、1Pa（5、10dyn／cm^2）的剪切应力处理培养的肾小管上皮细胞，分别作用1、3、6h后，用RT-PCR法检测megalin／cubilin mRNA的表达。结果剪切应力以大小、时间依赖性的方式下调肾小管上皮细胞megalin／cubilin mRNA的表达。结论DN早期流体剪切应力的增加可下调肾小管上皮细胞megalin／cubilin mRNA的表达，从而减少了肾小管对蛋白质的重吸收,表明DN早期微量白蛋白尿的发生可能与肾小管间质的早期损伤有关。Objective To study the effects of shear stress on the expression of megalin/cubilin mRNA in cultured renal tubular epithelial cells and explore the mechanism of tubulointerstitial damage in the early--stage of diabetic nephropathy （DN）. Methods The designed flow chamber had provided flow shear stress at 0.5,1 Pa （5 and 10 dyn/cm^2 ） for a period of 1 h,3 h and 6 h respectively. Semi-quantitive RT-PCR was used to detect the expression of megalin/cubilin mRNA in cultured renal tubular epithelial cells. Results The shear stress had down-regulated the expression of megalin/cubilin mRNA in cultured renal tubular epithelial cells in a magnitudeand fine-dependent way. Conclusion These results suggest that the increased tubular flow shear stress in the early-stage DN down regulates megalin/cubilin mRNA expression in renal proximal tubular cells and results in microalbuminuria. It is demonstrated that the shear stress could be one of the determinants in tubulointerstitial lesion occurrence during the progression of DN.

关 键 词：剪切应力 MEGALIN CUBILIN 

分 类 号：R318.01[医药卫生—生物医学工程]