基于内质网应激信号通路探讨阻断RAS在急性肝衰竭中的作用及机制

Recent researches have shown that local RAS of the liver is closely related to the occurrence and development of chronic hepatitis, cirrhosis and liver cancer. However, very few studies have proved the function of RAS in acute liver failure. Our previous studies have found that RAS blockage can significantly reduce the liver inflammation and inhibit the apoptosis of hepatocytes in acute liver failure rats, which may be related to the endoplasmic reticulum stress signaling pathway. In this study, we comprehensively assess the effect of RAS blockage on inflammation reaction, apoptosis and endoplasmic reticulum stress signaling pathway related molecules in rat liver using a D-GalN/LPS induced acute liver failure animal model, and elucidate the molecular mechanism of Ang-II induced endoplasmic reticulum stress signaling pathway using primary cultured liver cells in vitro, which may provide new ideas and theoretical basis for the treatment of acute liver failure.

肝脏局部的肾素-血管紧张素系统(RAS)与慢性肝炎、肝硬化及肝癌的发生发展密不可分，但尚缺乏其在急性肝衰竭中作用的研究。我们前期的研究发现，阻断RAS可以显著减轻急性肝衰竭大鼠的肝脏炎症，抑制肝细胞的凋亡，其机制可能与内质网应激信号通路有关。本研究通过D-GalN/LPS构建急性肝衰竭大鼠模型，全面评估阻断RAS对大鼠肝脏炎症、凋亡及内质网应激信号通路相关分子的影响，并利用体外培养原代肝细胞，阐明Ang-II通过内质网应激信号通路诱导肝细胞凋亡的分子机制，为急性肝衰竭的治疗提供新思路和理论依据。