阿托伐他汀通过 ERK1/2 通路改善急性心肌梗死后大鼠的心脏功能。
Atorvastatin improves the cardiac function of rats after acute myocardial infarction through ERK1/2 pathway.
机构信息
Department of Pharmacy, Shenzhen Longgang E.N.T. Hospital, Shenzhen, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):7120-7127. doi: 10.26355/eurrev_201908_18757.
OBJECTIVE
To study the regulatory effect of atorvastatin (ATV) on the extracellular signal-regulated kinase (ERK) 1/2 pathway and explore its effect on acute myocardial infarction (AMI) rats.
MATERIALS AND METHODS
The rat model of AMI was established, and the model rats were randomly divided into AMI group and ATV-AMI group, and Sham group was also set up. At 4 weeks after successful modeling, the cardiac function indexes of Sprague-Dawley (SD) rats were detected via magnetic resonance imaging (MRI) and echocardiography (ECG). After the rats were executed, the left ventricular weight index (LVWI) was measured, and the myocardial damage was detected via hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the messenger ribonucleic acid (mRNA) expressions of collagen I and collagen III in myocardial tissues were detected via Real Time-Polymerase Chain Reaction (PCR), and the expressions of ERK1/2 pathway-related proteins in myocardial tissues were detected via Western blotting.
RESULTS
After administration of ATV for AMI, the fractional shortening (FS%) and ejection fraction (EF%) were significantly restored. Compared with that in ATV-AMI group, LVWI was significantly increased in AMI group (p<0.05), indicating that ATV could improve the cardiac function after AMI. The results of HE staining and TUNEL staining showed that ATV-AMI group had slighter myocardial damage and significantly lower apoptosis rate than AMI group, indicating that ATV could reverse AMI through the ERK1/2 pathway. Besides, the mRNA expressions of collagen I and collagen III were higher in AMI group and ATV-AMI group than those in Sham group (p<0.05), while they were significantly lower in ATV-AMI group than those in AMI group (p<0.05). The expressions of ERK1/2 pathway-related proteins were also higher in AMI group and ATV-AMI group than those in Sham group (p<0.05).
CONCLUSIONS
ATV can significantly improve the cardiac function of SD rats after AMI, whose mechanism is related to the expression of the ERK1/2 pathway.
目的
研究阿托伐他汀（ATV）对细胞外信号调节激酶（ERK）1/2 通路的调节作用，并探讨其对急性心肌梗死（AMI）大鼠的影响。
材料与方法
建立 AMI 大鼠模型，将模型大鼠随机分为 AMI 组和 ATV-AMI 组，同时设立 Sham 组。成功建模 4 周后，通过磁共振成像（MRI）和超声心动图（ECG）检测 Sprague-Dawley（SD）大鼠的心脏功能指标。处死大鼠后，测量左心室重量指数（LVWI），通过苏木精-伊红（HE）染色和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色检测心肌损伤。此外，通过实时聚合酶链反应（PCR）检测心肌组织中胶原 I 和胶原 III 的信使核糖核酸（mRNA）表达，通过 Western blot 检测心肌组织中 ERK1/2 通路相关蛋白的表达。
结果
在给予 ATV 治疗 AMI 后，短轴缩短率（FS%）和射血分数（EF%）明显恢复。与 ATV-AMI 组相比，AMI 组的 LVWI 明显增加（p<0.05），表明 ATV 可改善 AMI 后的心脏功能。HE 染色和 TUNEL 染色结果显示，ATV-AMI 组心肌损伤较轻，细胞凋亡率明显低于 AMI 组，表明 ATV 可通过 ERK1/2 通路逆转 AMI。此外，与 Sham 组相比，AMI 组和 ATV-AMI 组的胶原 I 和胶原 III 的 mRNA 表达水平较高（p<0.05），而 ATV-AMI 组的表达水平明显低于 AMI 组（p<0.05）。ERK1/2 通路相关蛋白的表达水平在 AMI 组和 ATV-AMI 组也高于 Sham 组（p<0.05）。
结论
ATV 可显著改善 AMI 后 SD 大鼠的心脏功能，其机制与 ERK1/2 通路的表达有关。
Zotero 插件