Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Department of Orthopedics, Changzheng Hospital Affiliated with Second Military Medical University, Shanghai 200003, P.R. China.
Mol Med Rep. 2019 Dec;20(6):5183-5189. doi: 10.3892/mmr.2019.10774. Epub 2019 Oct 29.
Dexmedetomidine (DEX), a highly specific and selective α2 adrenergic receptor agonist, has been demonstrated to possess potential cardioprotective effects. However, the mechanisms underlying this process remain to be fully illuminated. In the present study, a myocardial infarction (MI) animal model was generated by permanently ligating the left anterior descending coronary artery in mice. Cardiac function and collagen content were evaluated by transthoracic echocardiography and picrosirius red staining, respectively. Apoptosis was determined by the relative expression levels of Bax and Bcl‑2 and the myocardial caspase‑3 activity. Additionally, nicotinamide adenine dinucleotide phosphate oxidase (NOX)‑derived oxidative stress was evaluated by the relative expression of Nox2 and Nox4, along with the myocardial contents of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. It was demonstrated that intraperitoneal DEX treatment (20 µg/kg/day) improved the systolic function of the left ventricle, and decreased the fibrotic changes in post‑myocardial infarction mice, which was paralleled by a decrease in the levels of apoptosis. Subsequent experiments indicated that the restoration of redox signaling was achieved by DEX administration, and the over‑activation of NOXs, including Nox2 and Nox4, was markedly inhibited. In conclusion, this present study suggested that DEX was cardioprotective and limited the excess production of NOX‑derived ROS in ischemic heart disease, implying that DEX is a promising novel drug, especially for patients who have suffered MI.
右美托咪定（DEX）是一种高特异性和选择性的α2 肾上腺素能受体激动剂，已被证明具有潜在的心脏保护作用。然而，这一过程的机制仍有待充分阐明。在本研究中，通过永久性结扎小鼠的左前降支冠状动脉，建立心肌梗死（MI）动物模型。通过经胸超声心动图和苦味酸天狼猩红染色分别评估心功能和胶原含量。通过 Bax 和 Bcl-2 的相对表达水平以及心肌半胱天冬酶-3 活性来确定细胞凋亡。此外，通过 Nox2 和 Nox4 的相对表达以及丙二醛（MDA）和超氧化物歧化酶（SOD）活性的心肌含量来评估烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）衍生的氧化应激。结果表明，腹腔内 DEX 治疗（20μg/kg/天）改善了左心室的收缩功能，并减少了心肌梗死后小鼠的纤维化改变，同时细胞凋亡水平降低。随后的实验表明，DEX 给药可恢复氧化还原信号，显著抑制包括 Nox2 和 Nox4 在内的 NOX 过度激活。总之，本研究表明 DEX 具有心脏保护作用，并限制了缺血性心脏病中 NOX 衍生 ROS 的过度产生，这表明 DEX 是一种很有前途的新型药物，特别是对已患有 MI 的患者。
