Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University.
Qingpu Branch of Zhongshan Hospital, Fudan University.
Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):94-102. doi: 10.14715/cmb/2022.68.2.14.
The study aimed to investigate the influences of aldehyde dehydrogenase 2 (ALDH2) on cardiomyocyte apoptosis in heart failure (HF) rats through regulating the PTEN induced putative kinase 1 (PINK1)-Parkin signaling pathway-mediated mitophagy. The rat model of HF was established, and the rats were randomly divided into model group (HF model, n=20) and ALDH2 group (intervention with ALDH2, n=20), with a normal group (n=20) set. After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function index creatine kinase (CK) was measured, the status of myocardial tissue injury was determined using hematoxylin and eosin staining, and the apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The activity of ALDH2 was detected, and the expression levels of genes and proteins were measured through quantitative polymerase chain reaction (qPCR) and Western blotting assay. The model group had notably decreased fractional shortening (FS) and ejection fraction (EF) and remarkably increased left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) compared with the normal group (p<0.05). The activity of ALDH2 declined obviously in the model group. The myocardial tissue injury was severer in the model group, and the number of apoptotic cells in myocardial tissues was greater in the model group than that in other groups (p<0.05). The model group manifested higher expression levels of Caspase-3 and light chain 3 (LC3) than the ALDH2 group (p<0.05) but significantly lower expression levels of PINK1, Parkin and B-cell lymphoma-2 (Bcl-2) (p<0.05). In comparison with those in the model group, the protein expression levels of PINK1, Parkin and Bcl-2 in myocardial tissues were prominently higher in the ALDH2 group (p<0.05). ALDH2 can inhibit cardiomyocyte apoptosis in HF rats by activating the PINK1-Parkin signaling pathway-mediated mitophagy, which is conducive to the recovery of HF.
本研究旨在通过调节醛脱氢酶 2（ALDH2）诱导的蛋白激酶 1（PINK1）-Parkin 信号通路介导的线粒体自噬，探讨 ALDH2 对心力衰竭（HF）大鼠心肌细胞凋亡的影响。建立 HF 大鼠模型，将大鼠随机分为模型组（HF 模型，n=20）和 ALDH2 组（干预用 ALDH2，n=20），并设置正常组（n=20）。建模成功后，应用 MRI 和 ECG 检测大鼠心功能指标。测量心肌功能指标肌酸激酶（CK），苏木精和伊红染色检测心肌组织损伤情况，末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色观察细胞凋亡。检测 ALDH2 活性，通过实时定量聚合酶链反应（qPCR）和 Western blot 检测基因和蛋白的表达水平。与正常组相比，模型组的部分缩短（FS）和射血分数（EF）明显降低，左心室舒张末期直径（LVEDD）和左心室收缩末期直径（LVESD）明显增加（p<0.05）。模型组 ALDH2 活性明显下降。模型组心肌组织损伤更严重，心肌组织凋亡细胞数多于其他组（p<0.05）。与 ALDH2 组相比，模型组 Caspase-3 和轻链 3（LC3）的表达水平明显升高（p<0.05），但 PINK1、Parkin 和 B 细胞淋巴瘤-2（Bcl-2）的表达水平明显降低（p<0.05）。与模型组相比，ALDH2 组心肌组织中 PINK1、Parkin 和 Bcl-2 的蛋白表达水平明显升高（p<0.05）。ALDH2 通过激活 PINK1-Parkin 信号通路介导的线粒体自噬抑制 HF 大鼠心肌细胞凋亡，有利于 HF 的恢复。
