我国从事苯胺生产的工人较多，其患中毒性肝病的发病机制尚不清楚。有研究证实慢性肝脏损伤与细胞的死亡方式有关，我们课题组前期的研究表明，苯胺引起肝细胞凋亡，但Caspase抑制剂Z-YVAD-fmk不能够完全抑制，这提示我们苯胺引起的肝脏损伤中可能存在其他死亡通路。目前RIPK与细胞死亡方式的关系是目前国内外研究的热点，但是RIPK与苯胺所致肝脏损伤的关系，迄今国内外尚无报道。我们推测，在苯胺致肝脏损害过程中程序性坏死也有一定作用，并可能与RIPK、MLKL、NF-kB等信号转导途径有关。为证实这一假说，我们将采用细胞水平和动物实验研究，探讨苯胺对RIPK激活及相关通路的调控作用，并通过人群队列研究来进一步揭示RIPK在苯胺致肝脏损害发生中的作用机制和地位。本课题将从新的视觉阐明苯胺致肝脏损害的发病和发展机制，从而为苯胺中毒的生物学监测与预防提供科学依据，为苯胺引起肝脏损伤的防治提供新思路。

There are more workers who are engaged in aniline production in China and the pathogenesis of toxic liver disease is not clear.Studies have shown that chronic liver injury is associated with cell death pathways and we have confirmed that aniline could induce hepatocyte apoptosis,but the Caspase inhibitor Z-YVAD-fmk could not completely inhibite this process.It suggests that there may be other death pathways in liver injury induced by aniline.At present, the relationship between RIPK and cell death mode is a research hotspot at home and abroad.However, the relationship between RIPK and aniline induced liver injury has not been reported in the world.We speculate that necroptosis play a role in the process of liver damage caused by aniline and it may be associated with some signal transduction pathways such as RIPK, MLKL, NF-kB. To confirm this hypothesis, we will investigate the effects of aniline on RIPK activation and related pathways through in vitro and in vivo studies. Furthermore,the mechanism and the role of RIPK in the liver damage induced by aniline will be revealed by cohort study. This subject will elucidate the pathogenesis and development mechanism of liver injury induced by aniline from a new perspective, so as to provide scientific basis for biological monitoring and prevention of aniline poisoning,and provide new ideas for prevention and treatment of liver injury caused by aniline.