细胞珠蛋白对肝星状细胞氧化损伤的保护作用  

Role of cytoglobin in protecting hepatic stellate cells against oxidation induced damage

作　　者：吕颖慧[1,2] 王启钊[1,2] 李招发[1,2] 刁勇[1,2] 许瑞安[1,2] 

机构地区：[1]华侨大学分子药物学研究所,泉州362021 [2]分子药物教育部工程研究中心,泉州362021

出　　处：《生物工程学报》2011年第8期1174-1182,共9页Chinese Journal of Biotechnology

基　　金：福建科技厅重点项目(No.2010Y0036);华侨大学基本科研业务费专项基金(No.JB-ZR1133);泉州市科技计划项目(No.2007Z41)资助~~

摘　　要：为揭示细胞珠蛋白对肝星状细胞氧化损伤的保护作用及相关机制,通过siRNA干扰内源性细胞珠蛋白基因,利用重组细胞珠蛋白作用于完全活化的人肝星状细胞系LX-2及大鼠原代肝星状细胞,并在LX-2细胞内过表达细胞珠蛋白,考察在过氧化氢及铁过载两种不同作用机制的氧化反应模型中细胞的增殖性及细胞内超氧化物水平。结果表明内源性细胞珠蛋白对于两种氧化反应导致的肝星状细胞损伤都具有显著性的保护作用,证明其在活化肝星状细胞内的表达上调是其应对氧化应激的保护性措施;重组细胞珠蛋白不仅能保护完全活化的LX-2细胞免受氧化应激损伤,并且能抑制未完全活化的原代肝星状细胞过度增殖以及保护其被过度损伤;重组细胞珠蛋白对细胞内的活性氧清除效果不理想,可能与其进出细胞缺乏相应的主动运输机制有关。进一步在LX-2细胞内过表达细胞珠蛋白对无论是铁过载或是过氧化氢引起的氧化反应均能发挥较好的保护性作用。本研究为加速肝纤维化药物新靶点开发提供了理论依据。The aim of this study was to reveal the protection role and the related mechanism of cytoglobin on the oxidation induced hepatic stellate cell damage.We applied siRNA to interfere the endogenous cytoglobin gene,used recombinant cytoglobin protein to treat the completely activated human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells,or over-expressed cytoglobin protein in LX-2 cells.We used two different oxidative-stress related models,the hydrogen peroxide model and the iron-overload model in our experiments and investigated the proliferation status and the intracellular superoxide level of the cells.The results showed that endogenous cytoglobin exerted significant protective effects on hydrogen peroxide or iron-overload induced LX-2 cell damage,confirming that upregulation of cytoglobin was the protective response of activated hepatic stellate cells to oxidative stress.Recombinant cytoglobin protein could protect LX-2 cells from oxidation induced damage,and prevent primary rat hepatic stellate cells from excessive proliferation and injury.The cytoplasmic reactive oxygen species（ROS） scavenging capacity of the recombinant cytoglobin protein was not as good as its capacity in scavenging ROS outside the cells,likely owing to the lack of active transporting mechanisms.Intracellular over-expression of cytoglobin protein could exert significant protective effect on LX-2 cells treated with hydrogen peroxide or iron-overload.Our results would accelerate the exploitation of new anti-fibrotic targets.

关 键 词：细胞珠蛋白 肝星状细胞 过氧化氢 铁过载 肝纤维化 

分 类 号：R575.2[医药卫生—消化系统]