Bian Hongjun, Zhou Yi, Yu Bin, Shang Deya, Liu Fuli, Li Bin, Qi Jianni
Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Department of Health Care, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Mol Med Rep. 2017 Aug;16(2):2002-2008. doi: 10.3892/mmr.2017.6826. Epub 2017 Jun 21.
It has been previously reported that Rho‑kinase (ROCK) and poly ADP-ribose polymerase (PARP) serve critical roles in myocardial ischemia/reperfusion (I/R) injury. Studies have additionally demonstrated that the activation of ROCK and the expression of PARP are increased in I/R. However, the effect and mechanism of the two proteins remains to be fully elucidated in I/R. In addition, whether they can be influenced by each other is unclear. In the present study, it was demonstrated that ischemia followed by reperfusion resulted in a significant increase in ROCK and PARP. In addition, Y‑27632 (ROCK inhibitor) and 3‑aminobenzamide (3‑AB; PARP inhibitor) pretreatment rescued myocardial infarction size and cardiomyocyte apoptosis. The inhibitory role of Y‑27632 was observed to be superior to that of the 3‑AB group. In addition, Y‑27632 and 3‑AB diminished extracellular signal‑related kinase (ERK) phosphorylation and the production of tumor necrosis factor α and interleukin 6. Overall, the results of the present study suggested that the inhibition of ROCK leads to reduced myocardial infarction size and cardiomyocyte apoptosis via the PARP/ERK signaling pathway.
先前已有报道称,Rho激酶(ROCK)和聚ADP核糖聚合酶(PARP)在心肌缺血/再灌注(I/R)损伤中发挥关键作用。研究还表明,在I/R过程中ROCK的激活和PARP的表达会增加。然而,这两种蛋白在I/R中的作用和机制仍有待充分阐明。此外,它们是否会相互影响尚不清楚。在本研究中,结果表明缺血后再灌注会导致ROCK和PARP显著增加。此外,Y-27632(ROCK抑制剂)和3-氨基苯甲酰胺(3-AB;PARP抑制剂)预处理可挽救心肌梗死面积和心肌细胞凋亡。观察到Y-27632的抑制作用优于3-AB组。此外,Y-27632和3-AB可减少细胞外信号调节激酶(ERK)磷酸化以及肿瘤坏死因子α和白细胞介素6的产生。总体而言,本研究结果表明,抑制ROCK可通过PARP/ERK信号通路减少心肌梗死面积和心肌细胞凋亡。