氟伐他汀对晚期糖基化终产物诱导的人近端肾小管上皮细胞转分化的影响

目的：研究氟伐他汀对晚期糖基化终产物（AGE）诱导的人近端肾小管上皮细胞（HK-2）转分化的影响及核因子（NF）-κB在其中所起的作用。方法：将培养细胞分为5组：（1）BAS组;（2）AGE-BAS组;（3）AGE-BAS＋NF-κB特异性阻断剂（PDTC）组;（4）AGE-BAS＋氟伐他汀组;（5）AGE-BAS＋氟伐他汀＋PDTC组。应用EMSA法测定NF-κB活性变化。Westernblot法检测α-平滑肌肌动蛋白（α-SMA）、E-钙黏着糖蛋白（E-cadherin）表达。结果：氟伐他汀在一定浓度范围内,呈剂量依赖性抑制AGE-BSA诱导的HK-2细胞NF-κB活化。AGE-BSA刺激后随浓度增加,时间延长,α-SMA蛋白表达明显升高、E-adherin蛋白表达明显降低。NF-κB特异性阻断剂PDTC及氟伐他汀均能部分阻断AGE-BSA诱导的α-SMA蛋白表达升高及E-adherin蛋白表达降低。氟伐他汀＋PDTC进一步抑制AGE-BSA诱导的α-SMA蛋白表达升高及E-adherin蛋白表达降低。结论：NF-κB参与了AGE-BSA诱导的HK-2细胞转分化。氟伐他汀抑制HK-2细胞转分化除通过抑制NF-κB活化,可能还有其他机制。

Effects of Fluvastatin on Epithelial-to-Mesenchymal Transition in Human Proximal Tubular Epithelial Cells Induced by Advanced Oxidation Protein Products

Objective：To investigate the effects of fluvastatin on epithelial-to-mesenchymal transition and the role of nuclear factor（NF）-κB in human proximal tubular epithelial cells（HK-2）induced by advanced glycation end products（AGE）.Methods：Cultured cells were divided into five groups：（1）BAS group;（2）AGE-BAS group;（3）AGE-BAS＋NF-κB specific inhibitor（PDTC）group;（4）AGE-BAS＋fluvastatin group;（5）AGE-BAS＋fluvastatin＋PDTC group.EMSA was used to determin NF-κB activation.Western blot was used to detect he expression of α-smooth muscle actin（α-SMA）protein and E-cadherin protein.Results：Fluvastatin in a certain range of concentration inhibited NF-κB activation induced by AGE-BSA in HK-2 cells in a dose dependent.AGE-BSA significantly up-regulated the expression of α-SMA protein,whereas it down-regulated the expression of E-adherin protein.Either NF-κB specific inhibitor PDTC or fluvastatin can partly block the increase of expression of α-SMA protein and the decrease of expression of E-adherin protein.Fluvastatin＋PDTC further inhibited the increase of expression of α-SMA protein and the decrease of expression of E-adherin protein induced by AGE-BSA.Conclusion：NF-κB involved in the AGE-BSA-induced HK-2 cells transdifferentiation.Fluvastatin inhibited epithelial-to-mesenchymal transition via NF-κB-dependent and independent mechanisms.