Myocardial ischemia/reperfusion (MI/R) injury, a complicated pathophysiological process, is regulated by lots of signaling pathways. Here in our present study, we identified TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, as a protective regulator in MI/R injury. Our results indicated that TBK1 was decreased in MI/R injury in mice. However, after overexpressing TBK1 through an intramyocardial injection of TBK1 adenovirus, TBK1 overexpression improved cardiac function detected by echocardiography, decreased infarct size detected by Evans Blue and TTC staining, reduced cardiomyocyte apoptosis measured by TUNEL staining and alleviated disruption of mitochondria and cardiac muscle fibers detected by TEM in response to MI/R injury. Consistently, TBK1 overexpression ameliorated mitochondrial oxygen consumption rate (OCR) in neonatal rat cardiomyocytes (NRCMs) in response to hypoxia/reoxygenation (H/R) injury. Mechanistically, TBK1 overexpression upregulated Bcl-2 (an anti-apoptotic protein) but downregulated Bax (a pro-apoptotic protein) in vivo and in vitro. Collectively, our findings uncovered a pivotal function of TBK1 in MI/R injury through regulating the levels of apoptotic proteins for the first time, which might represent a promising target in treating MI/R patients in the future.

心肌缺血/再灌注（MI / R）损伤是一个复杂的病理生理过程，受许多信号通路的调节。在本研究中，我们确定了INK相关丝氨酸/苏氨酸激酶TANK结合激酶1（TBK1）是MI / R损伤的保护性调节因子。我们的结果表明，TBK1在小鼠MI / R损伤中降低。但是，通过心肌内注射TBK1腺病毒过表达TBK1后，TBK1过表达改善了通过超声心动图检测到的心脏功能，通过Evans Blue和TTC染色检测到的梗死面积减小，通过TUNEL染色检测到的心肌细胞凋亡减少，并减轻了检测到的线粒体和心肌纤维的破坏通过TEM响应MI / R损伤。一致地，TBK1过表达改善了新生大鼠心肌细胞（NRCM）对缺氧/复氧（H / R）损伤的线粒体耗氧率（OCR）。从机理上讲，在体内外，TBK1的过表达上调Bcl-2（一种抗凋亡蛋白），但下调Bax（一种促凋亡蛋白）。总的来说，我们的发现首次通过调节凋亡蛋白的水平揭示了TBK1在MI / R损伤中的关键作用，这可能是将来治疗MI / R患者的有希望的目标。