LncRNA-HOTAIR在氢气调控细胞自噬治疗大鼠急性胰腺炎中的作用机制研究

Acute pancreatitis (AP) is an inflammatory disease which is mainly characterized by self-digestion, edema, hemorrhage, and necrosis due to the trypsinogen activation in intro-acinar cells. Impaired autophagy plays the pivotal role in the pathogenesis of AP. LncRNA-HOTAIR could activate autophagy in the tumor cells，but its role in the inflammation is still unclear. The therapeutic effect of hydrogen gas (H2) on AP has been verified in our previous study, and we found that the H2 treatment inhibited autophagy in AP acinar cells. However the mechanism of regulating autophagy and the function of HOTAIR involved in this process require a more thorough investigation. In the present study, we attempt to carry out the experiments in vitro and in vivo to elucidate the role of autophagy involved in the therapeutic effect of H2 on AP, uncover the relationship between the expression of HOTAIR and the pathogenesis of AP, and interpret the main mechanism of HOTAIR on H2 modulating autophagy. Our project will reveal the pathogenesis of the early phase of AP more thoroughly, and provide new ideas and drug targets for the cure of AP.

急性胰腺炎（AP）是胰酶在腺体内被激活引起组织自身消化、水肿、出血甚至坏死的炎症反应。自噬的异常在其发病机制中具有重要作用。LncRNA-HOTAIR在肿瘤细胞中可激活自噬，但在炎症中作用尚不清楚。我们在前期研究中已经证实了氢气（H2）对AP的治疗作用，并发现了H2可以抑制AP腺泡细胞的自噬水平，但其调控自噬的具体作用机制以及是否与HOTAIR的作用有关，还未阐明。本课题拟通过细胞及动物模型，运用分子生物学及细胞转染等实验手段，明确自噬在H2治疗AP中的作用，揭示HOTAIR表达量与炎症反应之间的关系，以及探究H2对自噬的调控机制是否与HOTAIR有关等问题。以期通过本项研究更为深入地揭示AP早期阶段的发病机理，并为治疗提供新的靶点和思路。