Zhang Q, Lu L, Liang T, Liu M, Wang Z L, Zhang P Y
Bratisl Lek Listy. 2017;118(6):339-346. doi: 10.4149/BLL_2017_065.
To explore the role of the MAPK signaling pathway in the cardiomyocyte apoptosis of mice with post-infarction heart failure (HF).
Mice were divided into sham and myocardial infarction (MI) groups. Before surgery, the MI group was divided into SB203580 and PBS subgroups. A post-infarction HF model was established by ligating the left anterior descending coronary artery. Ventricular dilatation and cardiac function were observed by small animal echocardiography. The growth of primary cardiomyocytes was observed under an inverted phase contrast microscope. The mRNA and protein expressions of endoplasmic reticulum stress (ERS) markers, GRP78 and CHOP, were detected by qRT-PCR and immunofluorescence assay, respectively.
The MI group had enlarged left ventricle and decreased cardiac function. GRP78 and CHOP protein expressions in myocardial tissues, especially those of SB203580 subgroup, significantly increased (p < 0.05). The expressions of p-JNK and cleaved caspase 12 proteins, especially those of SB203580 subgroup, were significantly up-regulated. Cardiomyocytes of MI group were significantly more prone to apoptosis (p < 0.05), with SB203580 subgroup being more obvious.
MI was accompanied by ERS, probably involving the MAPK signaling pathway. SB203580, a specific inhibitor of this pathway, can relieve cardiomyocyte apoptosis and protect the myocardium by suppressing such stress (Tab. 3, Fig. 7, Ref. 20).
探讨丝裂原活化蛋白激酶（MAPK）信号通路在心肌梗死后心力衰竭（HF）小鼠心肌细胞凋亡中的作用。
将小鼠分为假手术组和心肌梗死（MI）组。手术前，MI组再分为SB203580组和PBS组。通过结扎左冠状动脉前降支建立心肌梗死后HF模型。采用小动物超声心动图观察心室扩张和心脏功能。在倒置相差显微镜下观察原代心肌细胞的生长情况。分别采用qRT-PCR和免疫荧光法检测内质网应激（ERS）标志物葡萄糖调节蛋白78（GRP78）和C/EBP同源蛋白（CHOP）的mRNA和蛋白表达。
MI组左心室扩大，心脏功能降低。心肌组织中GRP78和CHOP蛋白表达显著增加，尤其是SB203580组（p<0.05）。p-应激活化蛋白激酶（JNK）和裂解型半胱天冬酶12蛋白表达显著上调，尤其是SB203580组。MI组心肌细胞更容易发生凋亡（p<0.05），SB203580组更明显。
MI伴有ERS，可能涉及MAPK信号通路。该信号通路的特异性抑制剂SB203580可通过抑制这种应激减轻心肌细胞凋亡并保护心肌（表3，图7，参考文献20）。
