[1]何婷,管旭,孙蕾,等.白藜芦醇对高糖诱导的肾小管上皮细胞转分化的抑制作用[J].陆军军医大学学报(原第三军医大学学报),2014,36(15):1572-1576.
 He Ting,Guan Xu,Sun Lei,et al.Inhibitory role of resveratrol in high glucose-induced renal tubular epithelia-mesenchymal transition and its underlying mechanism[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(15):1572-1576.
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
36卷
期数:
2014年第15期
页码:
1572-1576
栏目:
论著
出版日期:
2014-08-15

文章信息/Info

Title:
Inhibitory role of resveratrol in high glucose-induced renal tubular epithelia-mesenchymal transition and its underlying mechanism
作者:
何婷管旭孙蕾杨可肖堂利徐新丽杨琴赵景宏
第三军医大学新桥医院肾内科
Author(s):
He Ting Guan Xu Sun Lei Yang Ke Xiao Tangli Xu Xinli Yang Qin Zhao Jinghong
Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
关键词:
白藜芦醇高糖上皮-间充质转分化NADPH氧化酶
Keywords:
resveratrol high glucose epithelia-mesenchymal transition NADPH oxidase
分类号:
R282.71; R322.61; R692
文献标志码:
A
摘要:
目的      探讨白藜芦醇对高糖诱导人肾小管上皮细胞(HK-2)发生上皮-间充质细胞转分化(epithelia-mesenchymal transition,EMT)的抑制作用及机制。      方法       体外培养HK-2细胞,分为正常对照组(NG,5.5 mmol/L)、高糖组(HG,30 mmol/L)、白藜芦醇组(RES,10 μmol/L)、高糖(30 mmol/L)+白藜芦醇(10 μmol/L)组(HG+RES)、二苯基碘(diphenyleneiodonium)组(DPI,10 μmol/L)、高糖(30 mmol/L)+DPI(10 μmol/L)组(HG+DPI)。倒置显微镜下观察高糖对细胞形态的影响。免疫荧光检测上皮细胞标志物波形蛋白(cytokeratin)及间充质细胞标志物波形蛋白(vimentin)的表达变化,Western blot检测α平滑肌肌动蛋白(α-SMA)、E钙黏蛋白(E-cadherin)、NADPH氧化酶亚基(NOXs)的表达变化,DCFH-DA法检测细胞内ROS水平。      结果       与正常对照组相比,高糖处理后的HK-2细胞失去原有形态,呈长梭形改变,上皮细胞标志物cytokeratin及E-cadherin表达明显减少,间充质细胞标志物vimentin及α-SMA表达明显升高(P<0.01),同时NADPH氧化酶亚基NOX1、NOX4表达明显升高(P<0.01),NOX2无明显变化,ROS产生明显增多[(1 723.82±303.97) vs (2 579.36±353.76),P<0.01],而加入白藜芦醇或NADPH氧化酶抑制剂DPI预孵育后,均能抑制高糖诱导的HK-2细胞EMT(P<0.01)和ROS[(1 803.36±199.54)或(1 837.45±266.83) vs (2 579.36±353.76),P<0.01]产生增多,并且白藜芦醇可以明显抑制高糖诱导的NOX1以及NOX4表达升高(P<0.01)。      结论       白藜芦醇可能通过抑制NADPH氧化酶降低肾小管上皮细胞ROS生成,进而抑制高糖状态下HK-2细胞EMT的发生。
Abstract:
Objective       To determine the effect of resveratrol on high glucose-induced epithelia-mesenchymal transition (EMT) of renal tubular epithelial cell line HK-2 and its underlying mechanism.       Methods         Cultured HK-2 cells were divided into 6 groups, that is, normal glucose (NG, 5.5 mmol/L), high glucose (HG, 30 mmol/L), resveratrol (RES, 10 μmol/L), high glucose and resveratrol (HG+RES, 30 mmol/L + 10 μmol/L), diphenyleneiodonium (DPI, NADPH oxdiase inhibitor, 10 μmol/L), and high glucose and DPI group (HG+DPI, 30 mmol/L + 10 μmol/L). Inverted microscopy was used to observe the morphological changes in high glucose-induced HK-2 cells. Expression of cytokeratin and vimentin was detected by immunofluorescence assay, and that of of α-smooth muscle actin (α-SMA), E-cadherin, NADPH oxdiase subunits (NOXs) were measured by Western blotting. Intracellular reactive oxide species (ROS) were detected by DCFH-DA fluorescence probe.       Results         After incubated with high glucose, HK-2 cells turned into long spindle-shape compared with NG group. Protein levels of epithelial markers E-cadherin and cytokeratin were significantly decreased, while those of the mesenchymal markers α-SMA and vimentin were increased (P<0.01). Protein levels of NADPH oxidase subunits NOX1 and NOX4 were significantly decreased (P<0.01), but that of NOX2 had no change, and intracellular ROS production was significantly increased (1 723.82±303.97 vs 2 579.36±353.76, P<0.01). The pre-incubation of resveratrol or DPI obviously inhibited EMT (P<0.01) and ROS production (1 803.36±199.54 and 1 837.45±266.83 vs 2 579.36±353.76, P<0.01) in HK-2cells induced by high glucose, while resveratrol markedly inhibited NOX1 and NOX4 expression (P<0.01).       Conclusion         Resveratrol may reduce ROS production through suppressing NADPH oxidase in renal epithelial cells, and thus inhibit the EMT of the cells induced by high glucose.

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更新日期/Last Update: 2014-07-25