Baicalin ameliorates H2O2 induced cytotoxicity in HK-2 cells through the inhibition of ER stress and the activation of Nrf2 signaling.
Baicalin ameliorates H2O2 induced cytotoxicity in HK-2 cells through the inhibition of ER stress and the activation of Nrf2 signaling.
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DOI：
10.3390/ijms150712507
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发表时间：
2014-07-15
影响因子：
5.6
通讯作者：
Zhu T
中科院分区：
文献类型：
--
作者：
Lin M;Li L;Zhang Y;Zheng L;Xu M;Rong R;Zhu T
肾缺血再灌注损伤在肾移植中起着关键作用，对移植肾的预后有很大影响。我们先前的研究证明，黄芩苷是从黄芩中分离出来的一种黄酮苷，对肾脏缺血再灌注损伤有保护作用。本研究旨在研究其在体外的作用机制。人肾近端小管上皮细胞系HK-2细胞在加入和不加入黄芩苷的条件下用过氧化氢刺激。检测细胞存活率、细胞凋亡率和氧化应激水平。用蛋白印迹和实时定量聚合酶链式反应分析内质网应激标志物结合免疫球蛋白(Bip)和C/EBP同源蛋白(CHOP)的表达。同时检测核因子-E2相关因子2(Nrf2)的表达。过氧化氢组细胞存活率下降，细胞凋亡率增加。活性氧(ROS)和谷胱甘肽/氧化谷胱甘肽(GSH/GSSG)分析显示氧化应激增加。内质网应激和Nrf2信号也增加。黄芩苷预处理可减轻H_2O_2诱导的细胞毒性，降低氧化应激和内质网应激，并进一步激活抗氧化Nrf2信号通路。内质网应激诱导剂和Nrf2抑制剂取消了这种保护作用，而内质网应激抑制剂和Nrf2诱导剂不能改善预后。本研究表明，黄芩苷对H_2O_2诱导的HK-2细胞毒性具有保护作用，其机制可能与抑制内质网应激和激活下游Nrf2信号有关。
Renal ischemia-reperfusion injury plays a key role in renal transplantation and greatly affects the outcome of allograft. Our previous study proved that Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, protects kidney from ischemia-reperfusion injury. This study aimed to study the underlying mechanism in vitro. Human renal proximal tubular epithelial cell line HK-2 cells were stimulated by H2O2 with and without Baicalin pretreatment. The cell viability, apoptosis and oxidative stress level were measured. The expression of endoplasmic reticulum (ER) stress hallmarks, such as binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP), were analyzed by western blot and real-time PCR. NF-E2-related factor 2 (Nrf2) expression was also measured. In the H2O2 group, cell viability decreased and cell apoptosis increased. Reactive Oxygen Species (ROS) and Glutathione/Oxidized Glutathione (GSH/GSSG) analysis revealed increased oxidative stress. ER stress and Nrf2 signaling also increased. Baicalin pretreatment ameliorated H2O2-induced cytotoxicity, reduced oxidative stress and ER stress and further activated the anti-oxidative Nrf2 signaling pathway. The inducer of ER stress and the inhibitor of Nrf2 abrogated the protective effects, while the inhibitor of ER stress and the inducer of Nrf2 did not improve the outcome. This study revealed that Baicalin pretreatment serves a protective role against H2O2-induced cytotoxicity in HK-2 cells, where the inhibition of ER stress and the activation of downstream Nrf2 signaling are involved.
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