Phenylephrine Attenuated Sepsis-Induced Cardiac Inflammation and Mitochondrial Injury Through an Effect on the PI3K/Akt Signaling Pathway
Phenylephrine Attenuated Sepsis-Induced Cardiac Inflammation and Mitochondrial Injury Through an Effect on the PI3K/Akt Signaling Pathway
复制标题
去氧肾上腺素通过影响 PI3K/Akt 信号通路减轻脓毒症引起的心脏炎症和线粒体损伤
DOI：
10.1097/fjc.0000000000000651
复制
发表时间：
2019-03-01
影响因子：
3
通讯作者：
Wang, Hua-dong
中科院分区：
文献类型：
--
作者：
Li, Hong-mei;Li, Kai-ying;Wang, Hua-dong
目的：探讨苯丙氨酸（PE）是否通过PI 3 K/Akt信号通路抑制脓毒症诱导的心功能不全、心肌炎症和线粒体损伤。方法：采用盲肠结扎穿孔法建立大鼠脓毒症模型。给予PE和/或渥曼青霉素（一种PI 3 K抑制剂）以研究PI 3 K/Akt信号传导在介导PE抑制脓毒症诱导的心功能不全、心脏炎症和线粒体损伤的作用中的作用。采用苏木精-伊红染色、超声心动图及Langendorff系统检测心肌损伤及功能。通过酶联免疫吸附试验分析TNF-α和IL-6的浓度。Western blotting分析细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）、髓过氧化物酶、血小板相关融合/分裂蛋白和PI 3 K/Akt信号通路相关蛋白。结果：PE可改善脓毒症大鼠心功能，提高存活率。PE可降低脓毒症大鼠心肌TNF-α、IL-6、ICAM-1、VCAM-1和髓过氧化物酶的含量。同时，PE使脓毒症大鼠心肌线粒体融合相关蛋白表达增加，分裂相关蛋白表达减少。PE激活了盲肠结扎穿孔大鼠的PI 3 K/Akt信号通路，并且PE的保护作用被wortmannin完全阻断。结论：PE通过PI 3 K/Akt信号通路减轻脓毒症诱导的心功能不全、心肌炎症和线粒体损伤。
Objective: To investigate whether phenylephrine (PE) inhibits sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway. Methods: A rat model of sepsis was established by cecal ligation and puncture. PE and/or wortmannin (a PI3K inhibitor) were administered to investigate the role of PI3K/Akt signaling in mediating the effects of PE on inhibiting sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury. Hematoxylin–eosin staining, echocardiography, and Langendorff system were used to examine the myocardial injury and function. The concentrations of TNF-&agr; and IL-6 were analyzed by enzyme-linked immunosorbent assay. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, mitochondria-related fusion/fission proteins, and PI3K/Akt signaling pathway–associated proteins were analyzed by Western blotting. Results: PE improved the cardiac function and survival in septic rats. PE decreased TNF-&agr;, IL-6, ICAM-1, VCAM-1, and myeloperoxidase contents in the myocardium of septic rats. Meanwhile, PE increased the fusion-related proteins and decreased the fission-related proteins in the myocardial mitochondria of septic rats. On the other hand, PE activated the PI3K/Akt signaling pathway in the cecal ligation and puncture–treated rats, and all the protective effects of PE were abolished by wortmannin. Conclusions: PE attenuated sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.