role of endoplasmic reticulum stress in acetaminophen-induced liver injury

本研究旨在探讨内质网应激在对乙酰氨基酚所致小鼠肝损伤中的作用。我们用ERAI （ER应激激活指示剂）转基因小鼠证明了APAP注射诱导肝脏Xbp1 mRNA剪接。此外，我们证明了C/EBP同源蛋白，一种内质网应激相关转录因子，与野生型小鼠相比，对APAP诱导的肝毒性小鼠具有保护作用。此外，我们还发现内质网应激抑制剂4-苯基丁酸（4-PBA）可显著减轻apap诱导的小鼠肝损伤。这些结果表明内质网应激在APAP肝毒性小鼠的发展中起重要作用，并提示内质网应激抑制是一种很有前景的治疗APAP肝损伤的策略。

This study was conducted to evaluate the role of endoplasmic reticulum (ER) stress in acetaminophen-induced liver injury in mice. We demonstrated the hepatic Xbp1 mRNA splicing induction by APAP injection using ERAI (ER stress activated indicator) transgenic mice. In addition, we proved that C/EBP homologous protein, an ER stress related-transcriptional factor, null mice were protected from APAP induced hepatotoxicity compared with wild-type mice. Furthermore, we also found that 4-phenylbutyric acid (4-PBA), an ER stress suppressor, significantly attenuated the APAP-induced liver injury in mice. These results indicate that ER stress plays important role in the development of APAP hepatotoxicity in mice, and suggest that ER stress suppression is a promising therapeutic strategy against APAP-induced liver injury.