自噬体不能成熟而导致的自噬过程中断，是心肌缺血/再灌注(I/R)损伤的重要机制，而miR-27a/Rubicon信号对自噬体成熟至关重要。 HSPA12B是特异性表达于血管内皮细胞的基因。我们在前一项国家自然基金研究中发现：内皮细胞高表达HSPA12B不仅改善I/R鼠心功能，且降低心肌Rubicon表达、升高内皮细胞exosome中miR-27a含量，提示HSPA12B可能通过exosome负载的miR-27a激活心肌细胞Rubicon/自噬体成熟信号，从而减轻心肌I/R损伤。 本项目将在前期工作基础上，采用HSPA12B转基因鼠、敲除鼠，综合评价内皮细胞HSPA12B对心肌I/R损伤的保护作用，并结合细胞模型，阐明 "exosome/miR-27a/Rubicon/自噬体成熟"信号系统在其中的作用，以明确保护机制。研究结果将从细胞间信号传递的角度，为心肌I/R损伤的临床防治提供新思路。

Impaired autophagic clearance resulted from disrupted autophagic maturation is a critical mechanism for the development of cardiac ischemia/reperfusion (I/R) injury. miR-27a/Rubicon signaling is important for autophagic maturation. HSPA12B is expressed specificly in endothial cells. During the former NSFC experiments, we observed that overexpression of HSPA12B in endothelial cells not only improved cardiac dysfunction,but also reversed the myocardial Rubicon induction and increased miR-27a content in endothelial cells - derived exosomes in cardiac I/R mice.These observations indicate that the cardioprotection of endothelial HSPA12B may mediated by miR-27a, which is transported from endothelial cells to cardiomyocytes by exosomes. To evaluate this posibility, we will eaxmined cardiac injury in HSPA12B transgenic mice and knockout mice following I/R. We will also determined whether the "exosome/miR-27a/Rubicon/autophgic maturation" signaling mediate the cardioprotection of HSPA12B using cell culture models. The results will provide novel clues for discovering potential intervention targets for the manegement and treatment of cardiac I/R injury.