Department of Cardiology, Union Hospital, Fujian Medical University, Fujian, China
Balkan Med J. 2019 Jul 11;36(4):245-250. doi: 10.4274/balkanmedj.galenos.2019.2019.3.8. Epub 2019 May 29.
Nuclear factor-kB is highly activated in cardiovascular disorders. However, few articles have targeted at the role of nuclear factor-kB inhibitor in heart failure.
To evaluate the effects of nuclear factor-kB inhibitor pyrrolidine dithiocarbamate on cardiocyte apoptosis and cardiac function in a rat heart failure model.
Animal experiment.
A stable and reproducible rat heart failure model (n=64) was prepared by injecting homologous microthrombotic particles into the left ventricle of Sprague–Dawley rats while obstructing the ascending aorta to produce coronary microembolization. Rats with heart failure were randomized into untreated (HFu) and pyrrolidine dithiocarbamate-treated (HFp) groups; the latter received an intraperitoneal injection of pyrrolidine dithiocarbamate (100 mg/kg/day) 1 h prior to surgery as well as on postoperative days 1-7. The sham group comprised 32 Sprague–Dawley rats. Eight rats from each group were sacrificed on days 1, 3, 7, and 14 postoperatively. Masson’s trichrome staining was used to determine the micro-fibrotic area to indicate the severity of myocardial loss. Terminal transferase uridine triphosphate nick end labeling staining was used to detect apoptotic cardiomyocytes. Echocardiography and hemodynamics were performed to evaluate left ventricular function.
Rats with heart failure exhibited pathological changes evidenced by patchy myocardial fibrosis, remarkably elevated severity of myocardial loss, and persistently reduced left ventricular function. At the end of the study, compared with the HFu group, myocardial infarct size was reduced by 28% (p=0.001), cardiocyte apoptosis was suppressed (7.17%±1.47% vs 2.83%±0.75%, p<0.001), cardiac function parameters such as left ventricular ejection fraction (80%±4% vs 61%±6%), left ventricular + dP/dt max (4828±289 vs 2918±76 mmHg.s), left ventricular - dP/dt max (4398±269 vs 2481±365 mmHg.s), and left ventricular systolic pressure (126±13 vs 100±10 mmHg) were significantly increased, and left ventricular end-diastolic pressure was reduced (18±2 vs 13±1 mmHg) (p<0.001, for all) in the HFu group.
Our rat model can adequately mimic heart failure via coronary vessel embolization. Moreover, pyrrolidine dithiocarbamate treatment can reduce cardiocyte apoptosis and improve cardiac function, which may be beneficial for patients with heart failure secondary to myocardial infarction.
核因子-κB 在心血管疾病中高度激活。然而，很少有文章针对核因子-κB 抑制剂在心力衰竭中的作用。
评估核因子-κB 抑制剂吡咯烷二硫代氨基甲酸盐对大鼠心力衰竭模型中心肌细胞凋亡和心功能的影响。
动物实验。
通过向 Sprague-Dawley 大鼠左心室注射同源微血栓颗粒并阻塞升主动脉以产生冠状动脉微栓塞，制备稳定且可重复的大鼠心力衰竭模型（n=64）。心力衰竭大鼠随机分为未治疗（HFu）和吡咯烷二硫代氨基甲酸盐治疗（HFp）组；后者在术前 1 小时和术后第 1-7 天给予腹腔注射吡咯烷二硫代氨基甲酸盐（100mg/kg/天）。假手术组包括 32 只 Sprague-Dawley 大鼠。每组 8 只大鼠在术后第 1、3、7 和 14 天处死。Masson 三色染色用于确定微纤维化面积以指示心肌丢失的严重程度。末端转移酶尿嘧啶三磷酸核苷缺口末端标记染色用于检测凋亡的心肌细胞。超声心动图和血流动力学用于评估左心室功能。
心力衰竭大鼠表现出病理变化，表现为斑片状心肌纤维化、心肌丢失严重程度显著升高和左心室功能持续降低。在研究结束时，与 HFu 组相比，心肌梗死面积减少 28%（p=0.001），心肌细胞凋亡减少（7.17%±1.47% vs 2.83%±0.75%，p<0.001），心功能参数如左心室射血分数（80%±4% vs 61%±6%）、左心室+dp/dt max（4828±289 vs 2918±76mmHg·s）、左心室-dp/dt max（4398±269 vs 2481±365mmHg·s）和左心室收缩压（126±13 vs 100±10mmHg）显著升高，左心室舒张末期压降低（18±2 vs 13±1mmHg）（p<0.001，均）。
我们的大鼠模型通过冠状动脉血管栓塞可以充分模拟心力衰竭。此外，吡咯烷二硫代氨基甲酸盐治疗可减少心肌细胞凋亡并改善心功能，这可能对心肌梗死后心力衰竭患者有益。
