circRBFOX2介导硫氧环蛋白2保护缺血再灌注损伤心肌的作用和机制研究

缺血再灌注(IR)损伤心肌修复是当今难题、急需解决。氧化应激在IR损伤中起重要作用，我们发现抗氧化的硫氧还蛋白2(TRX2)能减轻IR损伤、保护心肌细胞，但具体机制未阐明；我们预实验基因测序发现TRX2过表达后circRBFOX2显著降低，在所检测circRNA中差异最显著；circRBFOX2可抑制miR-206表达；过表达miR-206时自噬相关蛋白ATG13明显下降。因此我们推测：TRX2可能通过抑制circRBFOX2使miR-206升高，进而靶向抑制ATG13、抑制自噬、保护心肌。据此，我们拟(1)在细胞和动物水平通过circRBFOX2、miR-206、ATG13沉默和过表达验证各自在TRX2保护IR损伤心肌中的作用，(2)阐明circRBFOX2、miR-206和ATG13的相互作用及circRBFOX2介导TRX2保护IR损伤的机制。为IR损伤防治提供新思路和理论基础。

Remedy of myocardial ischemia-reperfusion (IR) injury is a major issue to be addressed right now in which oxidative stress plays an important role. We found that antioxidant thioredoxin-2 (TRX2) can reduce IR injury and protect cardiomyocytes. However, the specific mechanism remains unclear. Our preliminary data showed that circRBFOX2 level was significantly decreased after TRX2 overexpression and its was the most significantly changed one in all of the detecting circRNA by gene sequencing. circRBFOX2 could inhibit the expression of miR-206, our pre-experiment also found that autophagy-related protein ATG13 was significantly decreased in the injured cardiomyocytes with miR-206 overexpression. Therefore, we hypothesized that TRX2 might up-regulate miR-206 by inhibiting circRBFOX2 expression and that the up-regulated miR-206 might target the suppressed ATG13 to further inhibit autophagy and thus protect myocardium. In this light, we plan: (1) to study the respective roles of circRBFOX2, miR-206, and ATG13 by silencing or overexpressing each of them in the process of TRX2-involved protection of myocardium against IR injury in vitro and in vivo; (2) to study the interaction and relationship among circRBFOX2, mir-206 and ATG13; and to elucidate the protection mechanism of myocardium against IR injury by circRBFOX2-mediated TRX2 . This study will provide new ideas and lay theoretical basis for the prevention of IR injury.