肝脏缺血再灌注（I/R）损伤是肝脏手术和肝移植中最常见、最严重也是最难于治疗的问题，过度的内质网应激又是I/R损伤中极为关键的原因之一。我们的前期研究发现miR-199a-5p可以通过抑制过度内质网应激而发挥肝脏保护作用，还发现肝脏I/R时上调的LncRNA AK054386可以靶向吸附miR-199a-5p使其迅速下调。但这是否为导致内质网应激失控的机制，正是本研究关注的问题。因此，我们拟利用小鼠部分肝I/R损伤模型和肝细胞缺氧/复氧模型，研究AK054386、miR-199a-5p和内质网应激相关分子互相作用关系，明确AK054386调控肝细胞持续内质网应激及细胞凋亡的作用及分子通路；探讨肝脏I/R引起AK054386上调的机制，并初步在体内验证干扰AK054386对肝脏I/R损伤的保护效果。为肝脏I/R损伤的机制及防治研究开拓新思路并奠定理论基础。

Hepatic ischemia reperfusion injury is a common and intractable problem during liver operation and liver transplantation, at present there is no drugs and methods can be satisfactorily used to reduce liver ischemia reperfusion injury. New research shows that, sustained endoplasmic reticulum stress and the unfolded protein response (UPR) may be a key factor in ischemia reperfusion injury, but the mechanism remains to be further elucidated. Our previous study found that miR-199a-5p can inhibit sustained endoplasmic reticulum stress, and miR-199a-5p is decreased in ischemia liver, but its downregulation mechanism and its significance has not been elucidated. Preliminary experiments also found, during the hepatic ischemia reperfusion injury, the upregulation of lncRNA AK054386 can adsorb the miR-199a-5p and result in its rapid decline, so we propose lncRNA AK054386 can regulate endoplasmic reticulum stress response and hepatic ischemia reperfusion injury by adsorbing the miR-199a-5. We intend to study the molecules changes of AK054386, miR-199a-5p and UPR pathway in liver cells in vitro and animal models in vivo, and then investigate the interaction of AK054386 and miR-199a-5p and its underlying mechanisms, and validate the AK054386 intervention effect in vivo. Our study may show a novel molecular mechanism of hepatic ischemia reperfusion injury and provide some new clinical prevention strategies in the furture.