Department of Physiology, Faculty of Medicine, Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Inflammation. 2020 Jun;43(3):1143-1156. doi: 10.1007/s10753-020-01201-4.
Chronic obstructive pulmonary disease (COPD) is one of the most important factors in the progress of cardiovascular disease (CVD) which is associated with limited airflow and alveolar demolition. The aim of this study is to investigate the possible protective effect of ellagic acid (EA), as a natural anti-oxidant, against pulmonary arterial hypertension (PAH) and development of lung and heart injuries induced by elastase. Sixty healthy male Sprague-Dawley rats (150-180 g) were divided into six groups: control (saline 0.9%, 1 ml/kg, by gavage), porcine pancreatic elastase (PPE) (25 UI/kg, intratracheal), EA (10, 15, and 30 mg/kg, gavage), PPE + EA (30 mg/kg, by gavage). Lead II electrocardiogram was used to evaluate the inotropic and chronotropic parameters of rat heart using Bio-Amp device and the LabChart software. The anti-oxidant levels (superoxide dismutase, catalase, and glutathione) and malondialdehyde were measured by appropriate kits, and right ventricular systolic pressure (RVSP) was recorded by the PowerLab system and measured by the LabChart software (ADInstruments). Elastase administration caused an increase in RVSP which was in line with elevated inflammatory cells and cytokines, as well as lipid peroxidation, and decreased anti-oxidant levels. Also, electrocardiogram parameters significantly changed in elastase group compared with control rats. Co-treatment with EA not only restored elastase-depleted anti-oxidant levels and prevented pulmonary arterial hypertension but also improved cardiac chronotropic and inotropic properties. Our results documented that elastase administration leads to pulmonary arterial hypertension and EA, as an anti-inflammatory and anti-oxidant factor, can protect development of lung and heart injuries induced by elastase.
慢性阻塞性肺疾病（COPD）是心血管疾病（CVD）进展的最重要因素之一，其与气流受限和肺泡破坏有关。本研究旨在探讨鞣花酸（EA）作为一种天然抗氧化剂，对弹性蛋白酶诱导的肺动脉高压（PAH）和肺、心损伤的可能保护作用。60 只健康雄性 Sprague-Dawley 大鼠（150-180g）分为 6 组：对照组（生理盐水 0.9%，1ml/kg，灌胃）、猪胰弹性蛋白酶（PPE）（25UI/kg，气管内滴注）、EA（10、15 和 30mg/kg，灌胃）、PPE+EA（30mg/kg，灌胃）。采用 Bio-Amp 设备和 LabChart 软件通过 II 导联心电图评估大鼠心脏的变力和变时参数。采用适当的试剂盒测定抗氧化水平（超氧化物歧化酶、过氧化氢酶和谷胱甘肽）和丙二醛，用 PowerLab 系统记录右心室收缩压（RVSP），并通过 LabChart 软件（ADInstruments）进行测量。弹性蛋白酶给药导致 RVSP 升高，与炎症细胞和细胞因子升高、脂质过氧化以及抗氧化水平降低一致。此外，与对照组大鼠相比，弹性酶组的心电图参数也发生了显著变化。EA 联合治疗不仅恢复了弹性酶耗竭的抗氧化水平，预防了肺动脉高压，而且改善了心脏变时和变力特性。我们的研究结果表明，弹性蛋白酶给药可导致肺动脉高压，而 EA 作为一种抗炎和抗氧化因子，可防止弹性蛋白酶诱导的肺和心脏损伤的发生。
