Department of Cardiology, Anning Branch, 940 Hospital of the Joint Service support Force of the Chinese People's Liberation Army, Gansu, 730070, China.
Cell Mol Biol (Noisy-le-grand). 2022 Apr 30;68(4):194-201. doi: 10.14715/cmb/2022.68.4.23.
The study aimed to observe the effect of rosuvastatin on myocardial apoptosis in hypertensive rats through the silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway. The spontaneously hypertensive rat (SHR) model was established, and the rats were randomly divided into the SHR group, Rosuvastatin group and Control group. The blood pressure, creatine kinase (CK) and other myocardial indexes in each group were detected, the cardiac function indexes of rats were determined using magnetic resonance imaging (MRI) and echocardiography (ECG), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in myocardial tissues were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis level of myocardial tissues was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the expression levels of the SIRT1/NF-κB signaling pathway and apoptosis genes and proteins in myocardial tissues in each group were detected via quantitative polymerase chain reaction (qPCR) and Western blotting. In the SHR group, the blood pressure, the levels of serum creatinine (CR) and CK were increased (p<0.05). In the SHR group, both fractional shortening (FS%) and ejection fraction (EF%) were obviously lower than those in the control group (p<0.05), while both left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) were higher than those in the control group (p<0.05), and the levels of TNF-α, IL-6 and myeloperoxidase (MPO) were increased (p<0.05). The number of apoptotic cells in myocardial tissues in the SHR group was larger than that in the other two groups (p<0.05). In the SHR group, the expression levels of Caspase3 and NF-κB were remarkably higher than those in the Rosuvastatin group (p<0.05), while the expression levels of Bcl-2 and SIRT1 were remarkably lower than those in the Rosuvastatin group (p<0.05). Rosuvastatin can inhibit myocardial apoptosis in hypertensive rats through up-regulating SIRT1 and down-regulating NF-κB.
本研究旨在通过沉默信息调节因子 1（SIRT1）/核因子-κB（NF-κB）信号通路观察瑞舒伐他汀对高血压大鼠心肌细胞凋亡的影响。建立自发性高血压大鼠（SHR）模型，将大鼠随机分为 SHR 组、瑞舒伐他汀组和对照组。检测各组大鼠血压、肌酸激酶（CK）等心肌指标，采用磁共振成像（MRI）和超声心动图（ECG）检测大鼠心功能指标，采用酶联免疫吸附试验（ELISA）检测心肌组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。此外，采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法（TUNEL）染色检测心肌组织的凋亡水平。最后，采用定量聚合酶链反应（qPCR）和 Western blot 检测各组大鼠心肌组织中 SIRT1/NF-κB 信号通路及凋亡相关基因和蛋白的表达水平。在 SHR 组，大鼠血压、血清肌酐（CR）和 CK 水平升高（p<0.05）。与对照组相比，SHR 组的短轴缩短率（FS%）和射血分数（EF%）明显降低（p<0.05），而左心室舒张末期直径（LVEDd）和左心室收缩末期直径（LVESd）均高于对照组（p<0.05），TNF-α、IL-6 和髓过氧化物酶（MPO）水平升高（p<0.05）。心肌组织中凋亡细胞数量多于其他两组（p<0.05）。与瑞舒伐他汀组相比，SHR 组 Caspase3 和 NF-κB 的表达水平显著升高（p<0.05），而 Bcl-2 和 SIRT1 的表达水平显著降低（p<0.05）。瑞舒伐他汀可通过上调 SIRT1 和下调 NF-κB 抑制高血压大鼠心肌细胞凋亡。
