PhD. Gansu Provincial Central Hospital - Department of Cardiology - Gansu Province, China.
PhD. Gansu Provincial Central Hospital - Department of Integrated Pediatric Medicine - Gansu Province, China.
Acta Cir Bras. 2022 Jul 22;37(4):e370407. doi: 10.1590/acb370407. eCollection 2022.
Myocardial ischemia/reperfusion (MI/R) injury refers to a pathological condition of treatment of myocardial infarction. Oxidative stress and inflammation are believed to be important mechanisms mediating MI/R injury. Kukoamine A (KuA), a sperm, is the main bioactive component extracted from the bark of goji berries. In this study, we wanted to investigate the possible effects of KuA on MI/R injury.
In this experiment, all rats were divided into sham operation group, MI/R group, KuA 10 mg + MI/R group, KuA 20 mg + MI/R group. After 120 min of ischemia/reperfusion treatment, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rates of rising and fall of left ventricular pressure (±dp/dtmax), and ischemic area were detected. Serum samples of rats in each group were collected. The enzyme activities of catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), levels of malondialdehyde (MDA), CK muscle/brain (CK-MB), tumor necrosis factor (TNF), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardium in each group was detected according to the instructions of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of mammalian target of glycogen synthase kinase-3β (GSH-3β) and protein kinase B (Akt) mRNA level in myocardial tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR).
MI/R rats showed a significant increase in oxidative stress and inflammation. In addition, we showed that KuA significantly improved the myocardial function such as LVSP, left ventricular ejection fraction, +dp/dt, and -dp/dt. Here, it attenuated dose-dependent histological damage in ischemia-reperfused myocardium, which is associated with the enzyme activities of SOD, GSH-PX, and levels of MDA, IL-6, TNF-α, L-1β.
KuA inhibited gene expression of Akt/GSK-3β, inflammation, oxidative stress and improved MR/I injury. Taken together, our results allowed us to better understand the pharmacological activity of KuA against MR/I injury.
心肌缺血/再灌注（MI/R）损伤是治疗心肌梗死的一种病理状态。氧化应激和炎症被认为是介导 MI/R 损伤的重要机制。库卡胺 A（KuA）是从枸杞树皮中提取的主要生物活性成分之一。在这项研究中，我们旨在研究 KuA 对 MI/R 损伤的可能影响。
在本实验中，所有大鼠均分为假手术组、MI/R 组、KuA10mg+MI/R 组和 KuA20mg+MI/R 组。缺血/再灌注治疗 120min 后，检测左心室收缩压（LVSP）、左心室舒张末期压（LVEDP）、左心室压力上升和下降的最大速率（±dp/dtmax）和缺血面积。收集各组大鼠血清样本。采用酶联免疫吸附试验（ELISA）检测各组大鼠血清中天冬氨酸转氨酶（AST）、肌酸激酶同工酶（CK-MB）、肌酸激酶（CK）、乳酸脱氢酶（LDH）、肌钙蛋白 I（cTnI）、肌红蛋白（Mb）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的酶活性。根据末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）检测试剂盒的说明，检测各组心肌细胞的凋亡情况。采用逆转录-聚合酶链反应（RT-PCR）检测心肌组织中哺乳动物雷帕霉素靶蛋白（mTOR）、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）、核糖体蛋白 S6 激酶（p70S6K）、真核起始因子 4E 结合蛋白 1（4EBP1）和细胞外调节蛋白激酶（ERK）mRNA 水平的表达。
MI/R 大鼠氧化应激和炎症明显增加。此外，我们还发现 KuA 能显著改善 LVSP、左心室射血分数、+dp/dt 和-dp/dt 等心肌功能。在这里，它以剂量依赖性的方式减轻缺血再灌注心肌的组织损伤，这与 SOD、GSH-PX 酶活性以及 MDA、IL-6、TNF-α、L-1β水平有关。
KuA 抑制 Akt/GSK-3β 基因表达、炎症、氧化应激，改善 MR/I 损伤。综上所述，我们的研究结果使我们能够更好地理解 KuA 对 MR/I 损伤的药理作用。
