香叶基香叶基丙酮通过HSP70和Akt/GSK-3β/eNOS途径减轻心肌缺血/再灌注损伤。
Geranylgeranylacetone attenuates myocardium ischemic/reperfusion injury through HSP70 and Akt/GSK-3β/eNOS pathway.
作者信息
Zhou Chunxia, Bai Jie, Jiang Chuan, Ye Lincai, Pan Yanjun, Zhang Haibo
机构信息
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
出版信息
Am J Transl Res. 2017 Feb 15;9(2):386-395. eCollection 2017.
Abstract
Early reperfusion of myocardial infarction area is the most effective and important therapy to acute myocardial infarction, but could induce reperfusion injury. Geranylgeranylacetone (GGA), an acyclic polyisoprenoid used as an oral anti-ulcer medication, has been reported to have protective effects on reperfusion injury. In the present study, we explored the protective effect of GGA against MIRI and the underlying mechanism. We pretreated rats with four daily GGA, and then observed its effects on heart function parameters following in situ ischemia/reperfusion. GGA exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ± (dP/dt) max and decreased LVDP. Oxidative injury and inflammatory response were also relieved by GGA. Western blot showed that the HSP70 protein expression and the Akt/GSK-3β/eNOS pathway were activated. The inhibition of HSP70 and the Akt/GSK-3β/eNOS pathway significantly reversed the protective effects of GGA on MIRI, indicating the involvements of HSP70 and the Akt/GSK-3β/eNOS pathway.
摘要
心肌梗死区域的早期再灌注是急性心肌梗死最有效且重要的治疗方法，但可能会引发再灌注损伤。香叶基香叶基丙酮（GGA）是一种用作口服抗溃疡药物的无环聚异戊二烯，据报道对再灌注损伤具有保护作用。在本研究中，我们探讨了GGA对心肌缺血再灌注损伤（MIRI）的保护作用及其潜在机制。我们每天给大鼠预处理四次GGA，然后观察其对原位缺血/再灌注后心脏功能参数的影响。GGA使心脏功能显著改善，表现为左心室收缩压（LVSP）、±（dp/dt）max增加，左心室舒张压（LVDP）降低。GGA还减轻了氧化损伤和炎症反应。蛋白质免疫印迹法显示热休克蛋白70（HSP70）蛋白表达以及Akt/糖原合成酶激酶-3β/内皮型一氧化氮合酶（Akt/GSK-3β/eNOS）通路被激活。抑制HSP70以及Akt/GSK-3β/eNOS通路可显著逆转GGA对MIRI的保护作用，表明HSP70以及Akt/GSK-3β/eNOS通路参与其中。
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