肝细胞焦亡是引起和加重肝脏缺血/再灌注损伤（I/R injury）过程中炎症反应的主要原因，线粒体损伤是引起该条件下细胞焦亡的主要机制。然而，目前临床上尚无有效的线粒体保护药物。我们在既往研究中发现，促炎症消退介质Maresin1有显著的线粒体保护作用，但其机制尚不清楚。我们后续研究又发现，Higd1a基因有强大线粒体保护功能，而Maresin1可能通过激活维甲酸相关孤核受体a(RORa)上调Higd1a基因的表达。因此，本课题假设：在肝脏I/R损伤过程中，使用Maresin1可通过激活RORa/Higd1a通路保护线粒体进而减少肝细胞焦亡，从而减轻肝脏的炎性损伤。本课题拟以RORa/Higd1a/线粒体通路为切入点，研究Maresin1、RORa及Higd1a的相互调控关系及其在线粒体损伤、细胞焦亡及肝脏I/R损伤中的具体作用及机制，为临床上研发新的治疗肝脏I/R损伤的药物提供理论依据。

Liver cell pyroptosis is one of the main reasons for uncontrolled inflammatory response during liver ischemia/reperfusion injury (I/R injury). And mitochondria damage is the primary cause of cell pyroptosis under this situation. However, there exist no effective drug to protect mitochondria. We had demonstrated that Maresine1, one of the specialized pro-resolving mediators, had strong mitochondria protective effects, but the exact mechanisms remained unknown. We had further found that the Higd1a gene could protect cells from I/R injury by protecting the mitochondria, and Maresin1 may induce the expression of Higd1a by activating its receptor-retinoid acid receptor related orphan receptor α (RORa). Our hypothesis is that Maresin1 could reduce liver I/R injury by decreasing cell pyroptosis through RORa/Higd1a/mitochondria pathway. In this study, we will evaluate the exact regulatory relationships between Maresin1, RORa and Higd1a. And we will evaluate the exact functions of Maresin1, RORa and Higd1a in regulating mitochondria functions and cell pyroptosis during I/R injury. This project will provide new insights to develop novel drugs to protect cells from I/R injury.