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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。
To reveal the protective effect of cell globin on oxidative damage of hepatic stellate cells and its related mechanisms, siRNA was used to interfere with the endogenous cell globin genes and recombinant cell globin was used to act on the fully activated human hepatic stellate cell line LX-2 and Rat primary hepatic stellate cells and overexpression of cell globin in LX-2 cells. The effects of hydrogen peroxide and iron overload on the cellular proliferation and intracellular superoxide oxidation Level. The results showed that endogenous cell globulins have a significant protective effect on the hepatic stellate cell injury induced by two kinds of oxidative reactions, and it is proved that the up-regulation of the expression in activated hepatic stellate cells is a protective measure against oxidative stress ; Recombinant cell globin can not only protect fully activated LX-2 cells from oxidative stress injury, but also inhibit the over-proliferation of incompletely activated primary hepatic stellate cells and protect them from excessive damage; Recombinant cell-globin to cells Within the active oxygen scavenging effect is not satisfactory, may be related to its lack of access to cells corresponding active transport mechanism. Further overexpression of cell globin in LX-2 cells can exert a good protective effect on the oxidation reaction caused by iron overload or hydrogen peroxide. This study provides a theoretical basis for accelerating the development of new targets of hepatic fibrosis drugs.