Objective To investigate the effect of advanced glycation end products (AGEs)on the permeability of glomerular endothelial cells (rGEnC)in rats and the role of mitochondrial dysfunction in this pathological process.Methods Primary cultured rGEnC were incubated with AGEs (80 mg/L)for 24 h.The changes in endothelial permeability were investigated by transendothelial electrical resistance and the flux of flu-orescein isothiocyanate-conjugated bovine serum albumin.MitoSOX kit was used to detect intracellular reactive oxygen species (ROS).Mitochondrial membrane potential (△Ψm)was measured by JC1 fluorescein staining.The generation of adenosine triphosphate (ATP)was evaluated by luciferase assay system.The expression of NF-E2-related factor 2 (Nrf2)was detected by western blotting.Results The monolayer permeability and the generation of ROS of rGEnC were increased by AGEs.Pretreatment with tert-Butyl-hydroquinone (tBHQ)(20μmol/L),N-acetylcysteine (NAC)(1 0 mmol/L)and anti-RAGE antibody (1 00 mg/L)could suppress the detrimental effect of AGEs.The decline of △Ψm,ATP and Nrf2 were induced by AGEs,whereas the decrea-ses of △Ψm and ATP could be blocked by pretreatment with anti-RAGE antibody and the decline of △Ψm and Nrf2 inhibited by tBHQ pretreatment.Conclusions AGEs can cause mitochondrial dysfunction,leading to el-evated levels of ROS,which contributes to increase of permeability in rGEnC.%目的：探讨晚期糖基化终产物（AGEs）对大鼠肾小球内皮细胞（rGEnC）通透性的影响及线粒体功能障碍在其中的作用。方法采用原代培养的 rGEnC，予 AGEs 80 mg／L 作用24 h，采用跨内皮细胞电阻抗和异硫氰酸荧光素标记的牛血清白蛋白滤过率观察通透性的变化，MitoSOX 试剂盒检测细胞内活性氧，JC-1荧光标记法检测线粒体膜电位（△Ψm），荧光素酶检测系统测定三磷酸腺苷（ATP）的生成，蛋白免疫印迹法检测 NF-E2相关因子2（Nrf2）的表达。结果AGEs 可引起 rGEnC 通透性升高，活性氧产生增加，采用叔丁基对苯二酚（tBHQ）（20μmol／L）、N-乙酰半胱氨酸（NAC）（10 mmol／L）和抗 AGE 受体抗体（100 mg／L）预处理后，上述 AGEs 作用被抑制。AGEs 可引起 rGEnC △Ψm 下降，ATP 和 Nrf2减少，而 anti-RAGE 抗体可抑制△Ψm 下降和 ATP 减少， tBHQ 则能抑制△Ψm 下降和 Nrf2减少。结论AGEs 可导致 rGEnC 线粒体功能障碍，引起活性氧产生增加，从而导致 rGEnC 间通透性增加。
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