丝氨酸/苏氨酸激酶 Polo-like kinase 1 促进脓毒症诱导的心肌功能障碍。
Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction.
机构信息
Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University, Beijing, China.
Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University, Beijing, China; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
出版信息
Int Immunopharmacol. 2023 Dec;125(Pt A):111074. doi: 10.1016/j.intimp.2023.111074. Epub 2023 Oct 23.
Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα). Plk-1 inhibition impeded NF-κB signal pathway activation in LPS-treated mouse hearts and NRCMs. Augmented Plk-1 is thus essential for the development of SIMD and is a druggable target for SIMD.
脓毒症相关性心肌功能障碍（SIMD）是脓毒症患者死亡的主要原因。在这项研究中，我们发现 Polo 样激酶 1（Plk-1）是 SIMD 的一个促进因素。脂多糖（LPS）处理的小鼠心脏和新生大鼠心肌细胞（NRCMs）中 Plk-1 的表达增加。Plk-1 的抑制作用，无论是通过 Plk-1 杂合缺失还是 Plk-1 抑制剂 BI 6727，都能减轻 LPS 诱导的心肌损伤、炎症和心功能障碍，从而提高 LPS 处理小鼠的存活率。Plk-1 被鉴定为 IKKα 抑制剂的激酶。Plk-1 抑制作用阻止了 LPS 处理的小鼠心脏和 NRCMs 中 NF-κB 信号通路的激活。因此，增强的 Plk-1 对于 SIMD 的发展是必不可少的，并且是 SIMD 的一个可用药靶。
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