药物性肝损伤（DILI）严重威胁患者用药安全，炎性细胞因子的释放介导了DILI发生。我们前期研究发现IL-22对DILI具有肝保护效应，但具体保护机制尚不完全明了。近来的研究发现氧应激在DILI发生中具有重要作用，并与促炎症因子产生交互作用。最新研究报道IL-22可抑制氧应激保护靶器官，STAT3等信号通路在IL-22保护效应中起关键作用，并且活化的STAT3对氧应激调控至关重要。据此，我们推断IL-22除了其经典的直接抑制炎性反应效应外，还可能通过激活STAT3抑制氧应激，进而减少氧应激所介导的炎性因子产生和释放，发挥其保护作用。本课题拟通过IL-22转基因、IL-22基因敲除、肝脏特异性STAT3基因敲除小鼠等制备的药物性肝损伤模型，了解IL-22、氧应激及炎性反应间的关联性，并最终明确IL-22抑制氧应激介导的炎性反应在保护药物性肝损伤中的治疗作用及相关机制。

Drug-induced liver injury (DILI) has seriously threatened the clinical drug safe administration. Release of inflammatory cytokine mediates the DILI development. Our previous findings showed that IL-22 plays a hepato-protective effect in DILI patients. However the mechanism of protection is still unknown. Recent studies demonstrate that oxidative stress is important in DILI onset, and has the cross-reaction with cytokine induction. Latest studies reported that IL-22 protects the organ via inhibition of oxidative stress, and STAT3 signal transduction plays a central role in the IL-22 protective effect. Thus, we speculate IL-22 might suppress oxidative stress by STAT3 activation leading to inhibit the inflammatory cytokine production and release, which protects liver from injury. In this study, IL-22 transgenic mice, IL-22 gene knock-out mice and liver-specific STAT3 gene knock-out mice will be used to establish drug-induced liver injury model, to investigate the relationship between IL-22, oxidative stress and inflammatory reaction, finally elucidate the therapeutic effect and its related mechanism of IL-22 in suppression of oxidative stress mediated inflammatory reaction.