中文摘要：

目的 研究在早期糖尿病肾病微量蛋白尿状态下足细胞内质网应激（ERS）对钙调神经素（CaN）表达的调控情况.方法 以6、9、12周龄的C57BLKS/JLepr db/db雄性小鼠为研究对象,同龄C57 BLKS/J Lepr db/m小鼠为对照,观察小鼠24h尿白蛋白量的变化,激光共聚焦法检测早期糖尿病肾病小鼠CaN、synaptopodin表达的变化.以永生小鼠足细胞系为体外研究对象,棕榈酸盐引起ERS或联用熊去氧胆酸阻断ERS时,采用RT-PCR法、激光共聚焦法和免疫印迹法检测CaN的表达变化.结果 db/db早期糖尿病肾病小鼠模型中,足细胞CaN的表达随尿白蛋白量增加逐渐升高,synaptopodin的表达随蛋白量增加而降低.体外培养小鼠足细胞CaN的表达随棕榈酸盐刺激浓度增加而增加,ERS阻断时CaN表达减少.结论 足细胞ERS在伴有微量白蛋白时对CaN的表达有正向调控作用.

英文摘要：

Objective To investigate the regulation of calcineurin （CaN） by endoplasmic reticulum stress （ERS） in podocytes in vitro and in vivo at the stage microalbuminuria in diabetic nehropathy （DN） . Methods The urinary albumin excretions of C57BLKS/JLepr db/db and db/m mice at the ages of 6, 9, and 12 weeks were measured. The expressions of CaN and synaptopodin of these mice were observed. In immortalized mouse podocytes, the expression of podocyte CaN incubated with different concentrations of paltimate was quanti- tatively determined by real-time PCR. The changes of CaN incubated with paltimate with or without ursodeoxy- cholic acid （UDCA） were analyzed by confocal microscopy and Western blotting. Results As urine protein in- creased, the expression of CaN was enhanced and the expression of synaptopodin was reduced in early stage DN db/db mice potocytes. In immortalized mouse podoeytes, as the concentrations of palmitate increased, CaN mRNA increased. By confocal microscopy, the fluorescence intensity of CaN increased in palmitate treatment group After co-incubation with palmitate and UDCA, the fluorescence intensity decreased. The similar results were shown by Western blotting. Conclusion At the stage of microalbuminuria in DN, ERS in podocytes up-regu- lates the expression of CaN.