为揭示kallistatin对肝星状细胞氧化损伤的保护作用及相关分子机制,本文以过氧化氢和铁过载为氧化模型,以大鼠原代肝星状细胞及完全活化的人肝星状细胞系LX-2为对象,研究了kallistatin在对肝星状细胞活力、超氧化物、NADPH和Akt、e NOS等分子的影响。实验结果显示,kallistatin既能避免肝星状细胞受氧化损伤,还能修复氧化应激造成的细胞损伤;其主要机制为kallistatin能清除细胞内的超氧化物、降低细胞内NADPH活力;另外,kallistatin还能激活Akt和e NOS等分子发挥抗氧化作用。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 present study was aimed to investigate the role and mechanisms of kallistatin in protection against oxidative stress-induced hepatic stellate cell damage. The effects of kallistatin on the viability, the intracellular superoxide level and Akt, e NOS molecules were investigated in human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells. Two different oxidative-stress related models, the hydrogen peroxide model and the iron-overload model were used in the experiments. The results show that kallistatin protected the hepatic stellate cells from oxidative damage and repaired the cell damage by oxidative stress. The main mechanism is antioxidant activity of kallistatin, which can remove the oxidized substances inside the cells. On the other way, kallistatin activates Akt and e NOS molecules to generate the antioxidant effect. Our results help to explore new anti-fibrotic targets.